Current Gene Therapy[JOURNAL]
Sun
200 papers
Identifying Basement Membrane-Related Diagnostic Biomarkers for Rheumatoid Arthritis Through Machine Learning.
Min L, Zhang C, Xu L … +4 more , Deng J, Wang H, Ren S, Chen C
Curr Gene Ther · 2026 Jul · PMID 42393882 · Publisher ↗
INTRODUCTION: Rheumatoid Arthritis (RA) is a common autoimmune disease. The Basement Membrane (BM) plays a critical structural role in tissues such as the kidneys and joints, and is often implicated in immune-related dis...
INTRODUCTION: Rheumatoid Arthritis (RA) is a common autoimmune disease. The Basement Membrane (BM) plays a critical structural role in tissues such as the kidneys and joints, and is often implicated in immune-related diseases. This study aims to explore the complex interactions between RA and the BM, and to identify potential diagnostic biomarkers. METHODS: The data used in this study were sourced from the Gene Expression Omnibus (GEO) database. We screened Differentially Expressed Genes (DEGs) related to BM by comparing RA tissue with normal tissue. Consensus clustering analysis was performed based on the features of the BM in RA tissue samples. Functional enrichment analyses, including Gene Ontology (GO) and KEGG pathway analysis, were performed on genes common to the different clusters. Three machine learning algorithms were used to screen for biomarkers, including LASSO, Random Forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The screening results were validated using the GSE77298 dataset and confirmed via qRT-PCR. In addition, molecular docking technology was applied to predict the binding potential between Schisandrin (SCH) and the candidate biomarkers SEL1L3 and SLAMF8. RESULTS: By integrating RA transcriptome data with BM-related genes, we identified two BMassociated molecular subtypes of RA, both of which exhibit distinct immune cell infiltration characteristics. By further implementing a combination of LASSO, RF, and SVM-RFE, SEL1L3 and SLAMF8 were identified as candidate diagnostic biomarkers. In the external validation set (GSE77298) and qRT-PCR experiments, both exhibited significant upregulation in RA tissue and excellent diagnostic efficacy. The AUC of SEL1L3 and SLAMF8 was 0.987 and 0.970, respectively, and molecular docking suggests that SCH binds stably to both. DISCUSSION: The research results indicate that molecular changes related to BM may play an important role in the pathogenesis of RA, particularly through immune regulation and tissue remodeling. Identifying different subtypes of BM-related RA highlights the heterogeneity of RA and may help improve disease classification and personalized diagnosis. SEL1L3 and SLAMF8 can serve as promising biomarkers for early RA detection and provide new insights into BM-related immune mechanisms. CONCLUSION: SEL1L3 and SLAMF8 are the first BM-associated RA diagnostic markers identified, providing new targets for early RA diagnosis and investigation of its molecular mechanisms.
A Multi-Gene Myofibroblast Framework Stratifies Prognostic and Immune Landscapes in HCC.
Bai L, Shi Q, Fu L
Curr Gene Ther · 2026 Jul · PMID 42393881 · Publisher ↗
INTRODUCTION: Myofibroblasts play a critical role in the progression of hepatocellular carcinoma (HCC), a major subtype of primary liver cancer. METHODS: Bulk RNA-seq data were analyzed to identify core genes of relevant...
INTRODUCTION: Myofibroblasts play a critical role in the progression of hepatocellular carcinoma (HCC), a major subtype of primary liver cancer. METHODS: Bulk RNA-seq data were analyzed to identify core genes of relevant cell subpopulations. Next, cell clustering was performed based on public scRNA-seq data of HCC. Using the R package CellChat, receptor-ligand communication networks between myofibroblasts and other cell subtypes were characterized. Hub genes within HCC myofibroblast subpopulations were screened via hdWGCNA. Subsequently, differentially expressed genes (DEGs) from the bulk analysis were intersected with these hub genes. Machine learning algorithms were employed to select key genes to construct a nomogram. Finally, correlations in immune cell infiltration were analyzed. RESULTS: Six major cell subpopulations were identified from the scRNA-seq data, with prominent crosstalk observed between myofibroblasts and hepatocytes. Using hdWGCNA, 10 myofibroblastassociated co-expression modules were obtained, five of which were identified as functionally key modules. By intersecting the module hub genes with HCC-related DEGs, 15 overlapping genes were obtained. From these, four key genes were ultimately selected by machine learning algorithms: plasmalemma vesicle-associated protein (PLVAP), retinol binding protein 7 (RBP7), NADH dehydrogenase (Ubiquinone) 1 Alpha subcomplex subunit 4-like 2 (NDUFA4L2), and tropomyosin 2 (Beta) (TPM2). A nomogram integrating 6 imaging-histological features and PLVAP expression exhibited robust prediction capacity. All gene expressions were positively correlated with the infiltration of regulatory T cells (Tregs) and macrophage M0 and negatively correlated with the infiltration of neutrophils and monocytes. DISCUSSION: Myofibroblasts participate in extensive intercellular crosstalk in the HCC microenvironment, suggesting the potential value of myofibroblast-related biomarkers in HCC therapy. CONCLUSION: In this study, hub genes associated with myofibroblast programs in HCC were identified using scRNA-seq and hdWGCNA.
Single-cell Transcriptomics Inference of Neutrophil-mast Cell Communication Programs in Periodontitis.
Liu L, Xue M
Curr Gene Ther · 2026 Jun · PMID 42316490 · Publisher ↗
INTRODUCTION: Neutrophil dysregulation is one of the main features of periodontitis (PD). This study delineated neutrophil heterogeneity and predicted potential communication of mast cells within the microenvironment of...
INTRODUCTION: Neutrophil dysregulation is one of the main features of periodontitis (PD). This study delineated neutrophil heterogeneity and predicted potential communication of mast cells within the microenvironment of PD using computational single-cell transcriptomics. METHODS: We analyzed a public scRNA-seq dataset (GSE171213) from gingival tissues of healthy controls, PD patients, and post-treatment patients. Data processing, clustering, and annotation were performed using Seurat and Harmony packages. Cell-cell communication was computationally inferred using CellChat and NicheNet packages, and transcriptional regulatory programs were predicted via SCENIC. HMC-1.2 mast cells were treated with TGFB1 and assessed for proliferation, migration, the level of VEGFA, IL-6, and TNF-α. RESULTS: Ten cell types in PD were identified. Two distinct transcriptional states of neutrophils were identified based on gene expression profiles. Cell-cell communication analysis predicted that Subtype 2, which was enriched for inflammatory and effector genes, exhibited stronger putative interactions with mast cells via ligand-receptor pairs such as IL6-(IL6R+IL6ST) and SEMA4D- PLXNB2. NicheNet-based analysis further inferred that neutrophil-derived TGFB1, OSM, and IL1B were associated with mast-cell target gene programs related to proliferation, migration, angiogenesis, and inflammatory responses. Finally, in vitro cell experiments indicated that TGFB1 inhibited proliferation but promoted migration and the expression of VEGFA, IL-6, and TNF-α. However, all effects were reversed by SB431542, confirming TGFBR1 dependence. DISCUSSION: This study delineated neutrophil transcriptional heterogeneity in PD and identified neutrophil- mast cell communication axes as a contributor to the inflammatory microenvironment in PD. CONCLUSION: Through computational analysis of single-cell transcriptomics, this study described two neutrophil states and their predicted interaction network with mast cells in PD, providing testable hypotheses for future mechanistic and translational studies.
GULP1 in Ovarian Cancer: Expression, Biological Function, and Clinical Significance.
Sun Z, Hu X, Huang D … +1 more , Wang Y
Curr Gene Ther · 2026 Jun · PMID 42311021 · Publisher ↗
INTRODUCTION: As an engulfment adapter for apoptotic clearance, GULP1 is related to tumor progression, but its role in ovarian cancer (OVCA) remains unclear. METHODS: GULP1 expression, copy number variations (CNVs), and...
INTRODUCTION: As an engulfment adapter for apoptotic clearance, GULP1 is related to tumor progression, but its role in ovarian cancer (OVCA) remains unclear. METHODS: GULP1 expression, copy number variations (CNVs), and their correlations were analyzed using datasets collected from The Cancer Genome Atlas (TCGA)-OVCA and the Gene Expression Profiling Interactive Analysis (GEPIA). Gene set enrichment analysis (GSEA), immune infiltration assessment, and drug sensitivity prediction were conducted to identify pathways enriched by GULP1 and to explore its potential association with drug sensitivity. The binding affinity of candidate drugs to GULP1 was evaluated through molecular docking. Finally, cellular assays were performed to explore the biological functions of GULP1 in OVCA cells. RESULTS: GULP1 was downregulated in OVCA, particularly in advanced stages. The GULP1 expression was associated with enrichment of hypoxia, EMT, angiogenesis, and TGFβ signaling, which were correlated with immune evasion. LFM-A13 demonstrated binding affinity for GULP1 (ΔG = -5.85 kcal/mol). Overexpression of GULP1 inhibited migration and invasion of A2780 and SK-OV-3 cells. Conversely, GULP1 knockdown exerted the opposite effects. DISCUSSION: This study explored the role of GULP1 in OVCA and analyzed its correlation with the immune microenvironment and key pathways. Molecular docking predicted LFM-A13 as a potential therapeutic agent for OVCA; however, its efficacy remains to be clinically verified. CONCLUSION: The current findings reveal GULP1 as a novel biomarker for OVCA progression and immune escape, highlighting its role in modulating the tumor microenvironment (TME). Targeting GULP1 with LFM-A13 may offer a potential strategy for OVCA precision therapy.
Single‑cell Transcriptomic Profiling of Bone Marrow Mesenchymal Stem Cells Reveals Lineage Heterogeneity and Dysregulated Osteoblast Genes in Osteoporosis Versus Osteoarthritis.
Wang H, Zhuang C, Ma T … +1 more , Lin H
Curr Gene Ther · 2026 Jun · PMID 42253197 · Publisher ↗
INTRODUCTION: Osteoporosis (OP) and osteoarthritis (OA) are two skeletal disorders characterized by disrupted bone homeostasis. Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has emerged as a promising t...
INTRODUCTION: Osteoporosis (OP) and osteoarthritis (OA) are two skeletal disorders characterized by disrupted bone homeostasis. Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has emerged as a promising therapeutic strategy for both conditions; however, the precise molecular mechanisms mediating their beneficial effects remain poorly defined. METHODS: The GSE147287 dataset containing scRNA-seq data from BM-MSCs from OA and OP patients was obtained. Dimensionality reduction and cell clustering were performed using the Seurat R package, pseudotime trajectory analysis was carried out with the Monocle 2 package, and transcription factor (TF)-target gene regulatory networks were inferred using the GENIE3 R package. RT-qPCR quantified mRNA levels in a rat OP model, which was established via bilateral ovariectomy. RESULTS: Nine distinct BM-MSC subtypes were classified. OP samples had higher osteocytes and neutrophils and lower macrophages, chondroblasts, monocytes, and plasma B cells than OA samples. Chondroblasts (4 clusters), 2/3 linked to autophagy, may drive OA-to-OP progression. Osteoblasts (the largest OP-OA difference) showed reduced osteoblast differentiation, downregulated Wnt pathway genes, and upregulated ossification genes in late stages. In the rat model, CAT, CHRDL1, RUNX1, ETS1, FOXO3, and TAL1 were dysregulated. DISCUSSION: OP and OA exhibit distinct BM-MSC lineage heterogeneity. OA-to-OP progression involves enhanced oxidative phosphorylation and reduced autophagy. Downregulated RUNX1 (inhibiting NF-κB/IL-6) and Wnt pathway in OP were consistent with previous findings, showing the potential to serve as biomarkers for predicting disease progression and therapy response. CONCLUSION: This study preliminarily examined BM-MSC lineage heterogeneity in OP and OA, clarifying the dynamic development, transcriptional regulation, and biological functions of chondrocytes and osteoblasts in these two bone diseases.
Surface Functionalization of 3D-Printed Porous Ti-6Al-4V Scaffolds with PDA‑mHA-Col I Composite Coating Drives Macrophage Polarization toward the M2 Phenotype and Promotes Immunomodulation: An In Vitro Study.
Han X, Yuan H, Xiao Y … +6 more , Tang Z, Tian G, Gao J, Cai Q, Lin L, Xu X
Curr Gene Ther · 2026 Jun · PMID 42253196 · Publisher ↗
OBJECTIVE: To devise a bioactive surface functionalization approach for 3D-printed Ti- 6Al-4V scaffolds that influences macrophage polarization towards the pro-reparative M2 phenotype, therefore enhancing immunomodulatio...
OBJECTIVE: To devise a bioactive surface functionalization approach for 3D-printed Ti- 6Al-4V scaffolds that influences macrophage polarization towards the pro-reparative M2 phenotype, therefore enhancing immunomodulation and facilitating good implant-soft tissue integration. METHODS: Porous Ti-6Al-4V scaffolds were produced by selective laser melting and then covered with a polydopamine-multi-element-doped hydroxyapatite-type I collagen (PDA-mHA-Col I) composite. The scaffolds' physicochemical characteristics were characterized. Murine RAW264.7 macrophages were cocultured with uncoated (T) or coated (TPMC) scaffolds. Cell viability, proliferation, apoptosis, adhesion, and polarization were assessed via CCK-8 tests, EdU staining, flow cytometry, phalloidin staining, ELISA, and qRT-PCR. The NF-κB, PI3K/Akt, and STAT6 signaling pathways were examined using Western blotting and targeted inhibitors. RESULTS: The PDA-mHA-Col I coating improved surface hydrophilicity while maintaining mechanical characteristics. XPS verified effective collagen immobilization, exhibiting a surface nitrogen concentration of 13.03%. The coating demonstrated stability after 7 days in PBS, retaining a nitrogen content of 11.74% and negligible titanium exposure. In comparison to the T group, the TPMC scaffold markedly enhanced macrophage adhesion, proliferation, and spreading, while diminishing apoptosis. It prompted M2 polarization, as shown by reduced expression of M1 markers (iNOS, CD86) and pro-inflammatory cytokines (TNF-α, IL-6), with elevated expression of M2 markers (Arg-1, CD206) and anti-inflammatory cytokines (IL-10, TGF-β1). The TPMC scaffold suppressed the phosphorylation of NF-κB p65 while simultaneously activating PI3K/Akt and STAT6 signaling pathways. The inhibition of PI3K or STAT6 somewhat mitigated the increase of M2 markers. DISCUSSION: The coating created a pro-healing milieu by inhibiting inflammatory signals and stimulating pro-reparative pathways, thus tackling a significant obstacle in oral and maxillofacial bone repair. CONCLUSIONS: The PDA-mHA-Col I composite coating facilitates macrophage M2 polarization by concurrently inhibiting NF-κB and activating PI3K/Akt/STAT6 signaling, presenting a viable immunomodulatory approach for oral and maxillofacial bone restoration.
Screening and Functional Study of Biomarkers Related to Cell-in-cell Structure in Stomach Adenocarcinoma.
Fang X, Gu X, Hou D … +3 more , Meng T, Gao Z, Xue M
Curr Gene Ther · 2026 May · PMID 42227543 · Publisher ↗
INTRODUCTION: A comprehensive study of Cell-In-Cell (CIC) structures in stomach adenocarcinoma (STAD) may facilitate the development of therapeutic strategies. METHODS: Enrichment analysis was conducted using ssGSEA. WGC...
INTRODUCTION: A comprehensive study of Cell-In-Cell (CIC) structures in stomach adenocarcinoma (STAD) may facilitate the development of therapeutic strategies. METHODS: Enrichment analysis was conducted using ssGSEA. WGCNA was used to identify hub genes, and Differentially Expressed Genes (DEGs) were screened by the DESeq2 package. Gene selected by both LASSO regression (glmnet package) and SVM-RFE algorithms (e1071 package) were intersected to develop a diagnostic model for STAD using the rms package. Immune infiltration of STAD samples was analyzed using CIBERSORT and ESTIMATE algorithms. Single-cell data were processed by Seurat package. Cell subpopulations were identified using the FindClusters function, and their marker genes were subsequently determined by FindAllMarkers, followed by in vitro functional validation. RESULTS: Five genes (MSR1, PDGFRB, COL8A1, PLA2G7, and FCGR3A) with AUC > 0.8 were identified as potential biomarkers for STAD and combined into a five-gene diagnostic model. Immune infiltration analysis showed that these genes were associated with T-cell and macrophage infiltration. Among the ten cell types identified by single-cell analysis, the five biomarkers were found to be highly expressed specifically in macrophages and fibroblasts. In vitro functional assays confirmed that these markers were upregulated in HGC-27 and AGS cells, and that MSR1 regulated STAD cell proliferation, migration, and invasion. DISCUSSION: The five biomarkers, which showed a specifically high expression in macrophages and fibroblasts, were closely associated with heterotypic CIC formation. Further analysis suggested that these biomarkers contributed to STAD pathogenesis, potentially via immune, stromal, and metabolic crosstalk. These findings help clarify the interactions between CIC biology and the STAD tumorimmune microenvironment. CONCLUSIONS: The five biomarkers provide valuable insights for the early screening, diagnosis, and treatment of STAD.
HOXC4 Is Associated with the Prognosis and Immune Cell Infiltration in the Progression of Prostate Cancer.
Chen Z, Wang D, Xie Y … +8 more , Fang Z, Wang J, Yu Z, Chen Z, Zou Y, Chen Z, Liu Q, Huang H
Curr Gene Ther · 2026 May · PMID 42227542 · Publisher ↗
INTRODUCTION: Members of the Homeobox (HOX) gene family, particularly HOXCs, may be implicated in the development and prognosis of prostate cancer (PCa), but the specific mechanisms remain unclear. METHODS: The clinical...
INTRODUCTION: Members of the Homeobox (HOX) gene family, particularly HOXCs, may be implicated in the development and prognosis of prostate cancer (PCa), but the specific mechanisms remain unclear. METHODS: The clinical and transcriptomic data from TCGA-PRAD and GSE70770 were collected to examine the impact of HOXC family members on progression-free survival (PFS) in PCa. Meanwhile, the mechanisms of HOXC family members in PCa and their relationship with patients' prognosis were systematically investigated by performing survival analysis, enrichment analysis, and COX regression analysis. This study also developed a prognostic model. Additionally, a qPCR assay was conducted to determine the mRNA level of HOXC family members in PCa cells. RESULTS: Upregulated expressions of HOXC4, HOXC5, HOXC12, and HOXC13 in PCa tissues were found to be correlated with a worse prognosis. A prognostic model incorporating HOXC4 expression level, T stage, and Gleason score was constructed, exhibiting excellent performance in predicting 1-, 3-, and 5-year PFS (average AUC > 0.7). Enrichment analysis showed that HOXC4, which was highly expressed in PCa cells, may be involved in the progression and invasion of PCa through pathways such as oxidative phosphorylation, PLK1 signaling, cell cycle, and DNA methylation. Further, ssGSEA showed that HOXC4 may affect immune cell infiltration in PCa tumors. DISCUSSION: HOXC4 was related to immune cell infiltration and pathway activation in PCa and confirmed to be a risk factor for the cancer prognosis. However, the specific molecular mechanisms of HOXC4 in PCa development still require further investigation. CONCLUSION: The HOXC4-based prognostic model may be an effective tool for assessing the prognosis of PCa patients.
Identification of Potential Biomarkers in Autism: PRELID2, MYO1B, LRCH2, LIFR, and RERG May Serve as Regulators in Synaptic Membrane-Integrating Interneurons.
Zhang W, Wang C, Zhao X … +4 more , Pang S, Zhao Z, Zhang G, Chen J
Curr Gene Ther · 2026 May · PMID 42227541 · Publisher ↗
BACKGROUND: Autism Spectrum Disorder (ASD) is a highly heterogeneous neurodevelopmental condition. Single-cell RNA sequencing (scRNA-seq) has revealed transcriptional disruptions, particularly in interneurons, yet their...
BACKGROUND: Autism Spectrum Disorder (ASD) is a highly heterogeneous neurodevelopmental condition. Single-cell RNA sequencing (scRNA-seq) has revealed transcriptional disruptions, particularly in interneurons, yet their subtypes and molecular signatures remain poorly understood. METHODS: It was analyzed scRNA-seq data from the human Prefrontal Cortex (PFC). Key cell types were identified using Scissor and ROGUE methods, followed by secondary clustering for subtype annotation. A signature matrix was established using CIBERSORTx to deconvolute the bulk transcriptomes and estimate cell type-specific proportions. Differential subtype proportions between ASD and control samples were compared to identify key cell subtypes. Differentially Expressed Genes (DEGs) from both the key subtype and bulk data were intersected to determine subtypespecific biomarkers, which were further assessed via molecular docking. RESULTS: Interneurons were identified as the most heterogeneous cell population in ASD-affected PFC and were further categorized into five subtypes. A signature matrix was then developed with CIBERSORTx to reflect the proportion of each cell type and subtype. Among the cell subtypes, synaptic membrane-integrating interneurons (SMI-IN) emerged as the key subtypes, which exhibited notable distinctions between the ASD and control samples. Furthermore, five potential biomarkers (PRELID2, MYO1B, LRCH2, LIFR, and RERG) were identified from the SMI-IN subtype. Finally, quercetin and coumestrol were predicted as potential therapeutic compounds targeting these biomarkers. Nevertheless, as all findings were obtained via computational analysis, further cellular and clinical experiments are required to validate these identified biomarkers and candidate compounds. DISCUSSION: This study focused on interneurons and identified SMI-IN as a key cell subtype and its potential biomarkers (PRELID2, MYO1B, LRCH2, LIFR, and RERG). CONCLUSION: The present findings provided new insights for ASD intervention.
APOL3 Orchestrates Metastasis and Enzalutamide Resistance via STAT3-DAB2IP Signaling in Prostate Cancer.
Wang Q, Zuo S, Chen L … +5 more , Wan F, Hong Z, Xu W, Hou W, Ye D
Curr Gene Ther · 2026 May · PMID 42220127 · Publisher ↗
BACKGROUND: In advanced Prostate Cancer (PCa), metastatic spread and the inevitable emergence of enzalutamide resistance represent major clinical hurdles. Although apolipoprotein L3 (APOL3) is linked to oncogenesis, its...
BACKGROUND: In advanced Prostate Cancer (PCa), metastatic spread and the inevitable emergence of enzalutamide resistance represent major clinical hurdles. Although apolipoprotein L3 (APOL3) is linked to oncogenesis, its precise mechanistic role in PCa progression and antiandrogen resistance, particularly its regulation of the STAT3-DAB2IP axis, remains largely unexplored. METHODS: Publicly available clinical datasets were analyzed to evaluate APOL3 expression and its prognostic value. The functional consequences of modulating APOL3 and DAB2IP levels were assessed using in vitro and in vivo PCa models, including an established enzalutamide-resistant cell line (C4-2R). Mechanistic insights into cellular proliferation, motility, angiogenesis, and drug response were derived from RNA sequencing, reciprocal co-immunoprecipitation (Co-IP), and dual-targeting phenotypic assays. RESULTS: APOL3 is significantly upregulated in PCa, strongly correlating with elevated Gleason scores, advanced stage, TP53 mutational status, and poor prognosis. Functionally, APOL3 promotes PCa proliferation, metastasis, and angiogenesis. Mechanistically, APOL3 sustains STAT3 phosphorylation and suppresses the tumor suppressor DAB2IP. Notably, Co-IP assays revealed a direct, bidirectional physical interaction between APOL3 and DAB2IP. Furthermore, we discovered that elevated APOL3 drives enzalutamide resistance not by enhancing classical Androgen Receptor (AR) activity, but by directly binding the Glucocorticoid Receptor (GR). This APOL3-GR complex activates a bypass signaling pathway entirely independent of the AR. While restoring DAB2IP resensitized cells to enzalutamide, it triggered a compensatory upregulation of APOL3. Consequently, concurrent APOL3 knockdown and DAB2IP overexpression yielded a powerful synergistic effect, profoundly dismantling malignant phenotypes, suppressing pro-metastatic markers (p-STAT3, VEGF, SNAIL, MMP2), and restoring enzalutamide sensitivity. DISCUSSION: These findings establish APOL3 as a central driver of prostate cancer metastasis and enzalutamide resistance. APOL3 drives these aggressive phenotypes by directly binding and suppressing DAB2IP to sustain oncogenic STAT3 signaling, and by activating an AR-independent bypass pathway through its physical interaction with the Glucocorticoid Receptor (GR). The enrichment of APOL3 in TP53-mutated and resistant tumors underscores its critical role in tumor plasticity. Consequently, synergistically co-targeting APOL3 alongside DAB2IP restoration represents a highly promising therapeutic strategy to overcome adaptive antiandrogen resistance and halt metastatic progression. CONCLUSION: APOL3 is a central driver of PCa aggressiveness and enzalutamide resistance, functioning via the direct modulation of the DAB2IP/STAT3 axis and the activation of the GR bypass pathway. Cotargeting APOL3 alongside DAB2IP restoration represents a highly promising, synergistic therapeutic strategy to circumvent adaptive resistance and halt metastatic progression in advanced castration-resistant prostate cancer.
A Telomere-Maintenance Three-Gene Model for the Prognostic Prediction in Intrahepatic Cholangiocarcinoma and Multi-Cohort Validation.
Wang L, Zhao W, Cui Z … +1 more , Li G
Curr Gene Ther · 2026 May · PMID 42220126 · Publisher ↗
INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is characterized by heterogeneity and poor survival. It remains unclear how telomere maintenance programs influence the prognosis and immune microenvironment in iCCA,...
INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is characterized by heterogeneity and poor survival. It remains unclear how telomere maintenance programs influence the prognosis and immune microenvironment in iCCA, and clinically applicable, telomere‑anchored transcriptomic tools are currently lacking. METHODS: Transcriptomes and survival data from TCGA-CHOL, GSE107943, and E-MTAB-6389 cohorts were integrated (n=135). Telomere maintenance gene (TMG) scores were calculated using GSVA and subsequently used for WGCNA module identification. Functional enrichment was analyzed with clusterProfiler (FDR-adjusted P < 0.05). A prognostic model was constructed using univariate Cox and LASSO-Cox regression analyses, and validated by Kaplan-Meier (KM) curve and time-dependent ROC. Immune features were inferred by MCPcounter, CIBERSORT, and ssGSEA algorithms. Drug sensitivity was predicted by pRRophetic, and the resulting IC50 estimates were then correlated with the RiskScore. RESULTS: The TMG score was inversely correlated with the ESTIMATE score (Spearman ρ=-0.2439, P=0.0044). WGCNA identified a TMG-associated module enriched for cellcycle/ mitotic and microtubule functions. Three key TMGs (PTTG1, TSPYL5, PLLP) were integrated to develop a RiskScore that can consistently stratify overall survival (OS) in both the integrated set and all external cohorts, demonstrating a robust accuracy for 1-, 3-, and 5-year prognostic prediction. High-RiskScore tumors exhibited reduced immune infiltration across multiple deconvolution frameworks. The RiskScore was negatively correlated with predicted IC50 for several agents (e.g., pyrimethamine, GNF-2, NSC-87877, CGP-082996, KIN001-135), suggesting higher drug sensitivity in high-risk cases. DISCUSSION: We identified a three-gene, telomere-related risk score for iCCA, which can effectively predict patients' survival and distinguish immune-cold, high-proliferation phenotypes. Potential targeted drugs for high-risk patients were predicted and supported by mechanistic validation. CONCLUSION: A compact telomere-anchored three-gene RiskScore was developed to predict the prognosis, immune contexture, and therapy sensitivity for iCCA.
Selecting Candidates for Genetic Therapy: A Patient-Centered Framework.
Henein M, Trakadis Y
Curr Gene Ther · 2026 Apr · PMID 42138146 · Publisher ↗
The rapid expansion of genetic therapies for the treatment of monogenic disorders represents one of the most transformative developments in contemporary medicine. Given the novelty, significant risks, and high costs of t...
The rapid expansion of genetic therapies for the treatment of monogenic disorders represents one of the most transformative developments in contemporary medicine. Given the novelty, significant risks, and high costs of these treatments, there is a need for a systematic approach to patient selection. We propose a patient-centered framework for identifying candidates for genetic therapy based on five key clinical questions and demonstrate its application through illustrative examples.
Macrophage-related Genes were Discovered by Applying Highdimensional Weighted Gene Co-expression Network Analysis as Biomarkers for Esophageal Squamous Cell Carcinoma.
Yang J, Zhou C, Kong W … +4 more , Yi L, Zeng Z, Wang Y, Wu B
Curr Gene Ther · 2026 May · PMID 42136238 · Publisher ↗
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) lacks effective early diagnostic markers. High-dimensional WGCNA (hdWGCNA) enables the systematic identification of macrophage-related signatures from single-cell d...
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) lacks effective early diagnostic markers. High-dimensional WGCNA (hdWGCNA) enables the systematic identification of macrophage-related signatures from single-cell data, offering a novel approach to discovering potential biomarkers for ESCC. METHODS: This study analyzed bulk transcriptomic datasets and a single‑cell RNA‑seq dataset from the Gene Expression Omnibus (GEO) database. Specifically, the GSE53625 dataset (179 ESCC and 179 matched normal samples) was a training cohort, while GSE20347 (17 ESCC and 17 normal samples) was an independent validation set. The single‑cell dataset GSE196756 (3 ESCC and 3 adjacent normal tissues) was processed to construct a cellular atlas. The CellChat package was used to assess the communication between macrophages and other cell subpopulations. Macrophage‑associated co‑expression modules were identified by hdWGCNA. Differentially expressed genes (DEGs) were screened with the limma package, and the intersection of DEGs and hub genes from hdWGCNA was further refined via LASSO and SVM-RFE algorithms to obtain candidate genes. Functional enrichment, immune infiltration, drug prediction, and molecular docking were subsequently performed. In vitro experiments were carried out to validate the expression and functional role of candidate genes in ESCC cell lines. RESULTS: Four macrophage‑related gene models consisting of TGFBI, FTL, GPNMB, and APOE were created and validated. These genes were significantly overexpressed in ESCC tissues and exhibited high diagnostic accuracy, reaching an AUC value >0.8 in both the training and independent validation cohorts. In vitro functional assays confirmed that silencing TGFBI suppressed ESCC cell proliferation, migration, and invasion. Enrichment analysis linked these genes to neutrophil activation and apoptosis pathways, and immune infiltration analysis further revealed their correlation with immunosuppressive cell subsets. Drug prediction yielded 190 candidate compounds, and molecular docking suggested potential binding of retinoic acid, rosiglitazone, and GDC‑0941 to the corresponding targets in ESCC. DISCUSSION: In this study, four characteristic genes (TGFBI, FTL, GPNMB, and APOE) were identified for the diagnosis of ESCC, contributing to the improvement of early detection of the cancer. CONCLUSION: The present findings contributed to the pathogenesis research, detection, and management of ESCC.
A Complement and Coagulation Cascade-Related Prognostic Signature Predicts Survival and Immune Landscape in Lung Adenocarcinoma.
He B, Zhu R, Li N … +1 more , Li W
Curr Gene Ther · 2026 May · PMID 42136237 · Publisher ↗
OBJECTIVE: To evaluate the prognostic value of complement and coagulation cascades (CCC) in lung adenocarcinoma (LUAD). METHODS: Transcriptomic and clinical data of LUAD were retrieved from public databases. Differential...
OBJECTIVE: To evaluate the prognostic value of complement and coagulation cascades (CCC) in lung adenocarcinoma (LUAD). METHODS: Transcriptomic and clinical data of LUAD were retrieved from public databases. Differentially Expressed Genes (DEGs) were identified via the limma R package, and WGCNA was used to screen gene modules strongly correlated with CCC enrichment scores. Functional enrichment analysis was conducted with clusterProfiler. Univariate and LASSO Cox regression analyses were applied to build a CCC-related prognostic risk model, and its performance was validated using Kaplan-Meier survival analysis and ROC curves. ESTIMATE, MCPcounter, GSVA, and pRRophetic algorithms assessed immune infiltration and drug sensitivity, while CCK-8, Transwell, and scratch-healing assays verified the regulatory effects of biomarkers on cancer cells. RESULTS: WGCNA identified brown modules that were significantly correlated with CCC scores; enrichment analysis showed that these genes mainly participated in NF-κB, B-cell receptor signaling, and T-cell differentiation pathways. Six key genes (CPS1, EPHB2, LARGE2, MS4A1, OAS3, S100P) were selected to construct the risk model, with the high-risk group exhibiting poorer overall survival and lower T/B-cell infiltration. Risk scores were positively correlated with Rapamycin and Phenformin IC50s but negatively correlated with FTI-277, BMS-509744, etc. EPHB2 inhibition suppressed lung cancer cell viability, migration, and invasion. DISCUSSION: This study systematically characterized the molecular features and prognostic significance of CCC-associated genes in LUAD, established a CCC-related risk model, and confirmed their tight association with immune infiltration and drug sensitivity. CONCLUSION: The findings provide a theoretical foundation for precise prognostic evaluation and personalized treatment of LUAD.
An Epithelial-Mesenchymal Transition-Based Prognostic Model for Survival Prediction in Lung Adenocarcinoma: COL5A2 and ZEB2.
Zhang P, Zhang P, Tao C … +4 more , Li M, Guo Z, Yu Z, Wang Y
Curr Gene Ther · 2026 May · PMID 42099137 · Publisher ↗
INTRODUCTION: High heterogeneity and complex molecular mechanisms of lung adenocarcinoma (LUAD) lead to significant variability in patient prognosis. Epithelial-mesenchymal transition (EMT) is decisive to treatment respo...
INTRODUCTION: High heterogeneity and complex molecular mechanisms of lung adenocarcinoma (LUAD) lead to significant variability in patient prognosis. Epithelial-mesenchymal transition (EMT) is decisive to treatment response and tumor prognosis, which suggests that developing an EMT-related gene model might facilitate the prognostic management of LUAD. METHODS: The RNA-seq, clinical information, and imaging data of LUAD patients were collected from public databases. EMT-related modules were clustered by performing WGCNA with the "WGCNA" package. Differentially expressed genes (DEGs) were identified using the "DESeq2" package. A RiskScore model was constructed via uni/multivariate Cox regression analyses and Lasso regression, implemented with the "survival" and "glmnet" packages. The prognostic performance was evaluated using the Receiver Operating Characteristic (ROC) curve with the "timeROC" package. The CIBERSORT algorithm was utilized to conduct immune infiltration analysis. Drug sensitivity analysis was performed with the "oncoPredict" R package, followed by employing GSEA_4.4.0 software to conduct GSEA. A nomogram model was developed utilizing the "rms" package. Finally, the expression and potential functions of the selected key genes were validated through cellular assays. RESULTS: A prognostic RiskScore model was developed based on two EMT-related genes (COL5A2 and ZEB2), which were identified through WGCNA and differential expression analysis. This model effectively classified LUAD patients into low- and high-risk categories, where those in the highrisk subgroup exhibited markedly reduced overall survival. Tumor immune microenvironment analysis revealed distinct infiltration patterns between the two risk groups. Notably, high-risk LUAD patients exhibited enrichment of oncogenic pathways, including EMT and E2F targets. Computational assessments further indicated that the high-risk group was associated with an increased possibility of immune evasion and lower sensitivity to certain chemotherapeutic agents. Additionally, a radiomics-based nomogram incorporating two CT features exhibited promising diagnostic performance. Finally, in vitro experiments demonstrated that silencing COL5A2 suppressed LUAD cell proliferation, migration, and invasion, confirming its oncogenic role in LUAD. DISCUSSION: The present work discovered and systematically validated the potential regulatory roles of COL5A2 and ZEB2 in LUAD progression. However, future prospective studies and experimental validations are still needed to confirm the clinical utility of the model. CONCLUSION: We developed an EMT-related prognostic model and a non-invasive assessment nomogram for LUAD patients, hoping to facilitate personalized therapy for LUAD.
Hutchinson-Gilford Progeria Syndrome: Genetic Insights, Clinical Challenges, and Innovative Therapeutic Approaches.
Pruthvi Raj R, Swetha BR, Thomas J
Curr Gene Ther · 2026 May · PMID 42099136 · Publisher ↗
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder caused by a de novo point mutation in the LMNA gene, resulting in progerin, an abnormal form of lamin A. Progerin disrupts the nuclear architecture,...
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder caused by a de novo point mutation in the LMNA gene, resulting in progerin, an abnormal form of lamin A. Progerin disrupts the nuclear architecture, impairs DNA repair, and alters gene expression, collectively leading to systemic premature aging. Diagnosis involves a clinical evaluation, along with genetic and radiological tests, for skeletal and cardiovascular abnormalities. To provide an overview of current and emerging therapeutic strategies for HGPS, with a focus on pharmacological, genetic, and interventional approaches aimed at mitigating disease progression and improving survival outcomes. Current treatment focuses on symptom relief and extending lifespan. Emerging therapies include gene editing, antisense oligonucleotides, ICMT inhibitors, and high-risk cardiovascular interventions. Recent studies highlight angiopoietin-2 as a potential target. Symptomatic management remains the mainstay of care, with lonafarnib, an FDA-approved farnesyltransferase inhibitor, demonstrating modest benefits in reducing progerin accumulation and improving survival. Novel approaches under investigation include gene editing techniques, antisense oligonucleotides, and inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT). Cardiovascular interventions such as transcatheter aortic valve replacement and ascending aortic constriction are being explored for high-risk patients. Recent studies also identify angiopoietin-2 modulation as a potential therapeutic avenue for vascular and skeletal repair. While lonafarnib provides modest clinical benefit, long-term management of HGPS will likely depend on advances in gene editing, RNA-based therapies, and targeted pharmacological strategies to reduce progerin toxicity. Further research is needed to enhance precision and safety in gene therapies and to explore new molecular targets for broader therapeutic impact.
Construction of a Vasculogenic Mimicry-related RiskScore Model to Assess Patient Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.
Zhai Y, Gu X, Huang D … +1 more , Xue M
Curr Gene Ther · 2026 Apr · PMID 42083941 · Publisher ↗
INTRODUCTION: Vasculogenic mimicry (VM) plays vital roles in tumor development that are closely relevant to patient adverse outcomes and chemoresistance. This study aimed to identify a novel VM-associated signature to fo...
INTRODUCTION: Vasculogenic mimicry (VM) plays vital roles in tumor development that are closely relevant to patient adverse outcomes and chemoresistance. This study aimed to identify a novel VM-associated signature to forecast the prognosis and immunotherapy response of head and neck squamous cell carcinoma (HNSC) patients. MATERIALS AND METHODS: HNSC samples were derived from TCGA and GEO databases. VM-related genes (VMGs) were acquired from previous literature. VMGs' score was estimated using the "GSVA" package. The critical gene module was recognized by the "WGCNA" package. Differentially expressed genes (DEGs) were determined utilizing the "limma" package, and functional enrichment analysis was conducted by the "clusterProfiler" package. Hereafter, employing univariate Cox, lasso Cox, and multivariate stepwise regression analysis, the independent prognostic VMGs were identified to develop the RiskScore model and verify their predictive performance. Moreover, the immune infiltration, immunotherapy response, and drug sensitivity were analyzed. Finally, the expression of the selected key genes was evaluated in vitro using qRT-PCR in HNSC lines. RESULTS: The tumor group showed a higher VMGs score than the normal group. 590 key module genes were recognized by WGCNA, and then intersected with 6160 DEGs to obtain 293 candidate genes that were mainly involved in the PI3K-Akt and extracellular matrix (ECM)-relevant pathways. Thereafter, 9 independent prognostic VMGs (CHSY1, TNFAIP6, PRELP, HTRA1, RNF144A, COL8A2, DCHS1, FMOD, NOSTRIN) in HNSC were identified and selected to establish a RiskScore model, with good robustness in predicting patient outcomes. Compared with the low-risk group, the high-risk group showed an adverse prognosis, lower immune infiltration, and worse immunotherapy response. Besides, RiskScore was negatively correlated with several chemotherapeutic drugs such as FTI-277, Obatoclax Mesylate, Embelin, etc. Experimental validation using qRT‑PCR confirmed that most of the signature genes (including CHSY1, TNFAIP6, HTRA1, COL8A2, FMOD) were significantly upregulated in an oral squamous cell carcinoma line compared to normal keratinocytes. DISCUSSION: Our present study established a novel 9-VMGs RiskScore to predict the prognosis, immune infiltration features, immunotherapy response, and drug sensitivity for HNSC patients. This study provided a theoretical foundation for further exploration of HNSC pathogenesis, contributing to personalized treatment and drug selection for HNSC. CONCLUSION: The VM-related RiskScore we developed serves as a reliable prognostic and predictive tool, providing valuable guidance for risk stratification and immunotherapy decision-making in HNSC patients.
Sotagliflozin Ameliorates LPS‑Induced Cardiomyocyte Injury by Regulating the PI3K‑Akt and Extracellular Matrix-Related Pathways.
Liao J, Wang C, Gao Q … +2 more , Tian W, Hu H
Curr Gene Ther · 2026 Apr · PMID 42083524 · Publisher ↗
OBJECTIVE: This study aimed to define the protective effects of sotagliflozin against lipopolysaccharide (LPS)-induced injury in H9C2 cardiomyocytes, and map the core molecular pathways driving these effects to support n...
OBJECTIVE: This study aimed to define the protective effects of sotagliflozin against lipopolysaccharide (LPS)-induced injury in H9C2 cardiomyocytes, and map the core molecular pathways driving these effects to support new therapeutic strategies for SRMI. METHODS: H9C2 rat cardiomyocytes were divided into a control group, LPS-challenged group, and LPS-challenged groups treated with 10, 20, and 30 μM sotagliflozin. Label-free quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) proteomics, coupled with bioinformatic analyses, was performed to map the drugregulated molecular network. Cell Counting Kit-8 (CCK-8) assay, biochemical kits, quantitative Real-Time PCR (qRT-PCR), Western blotting, immunofluorescence staining, and JC-1 probe assay were used to assess cell viability, cytotoxicity, oxidative stress markers, expression of inflammatory cytokines and NLRP3 inflammasome-related molecules, and mitochondrial membrane potential, respectively. RESULTS: Proteomic profiling quantified 10,270 stably expressed proteins across all samples. Principal Component Analysis (PCA) revealed that PC1 and PC2 cumulatively explained 50.33% of intergroup variance, with clear separation between control and LPS groups, a pattern partially reversed by sotagliflozin treatment. In total, 630 differentially expressed proteins (DEPs; 252 upregulated, 378 downregulated) were identified in the LPS vs control comparison, and 210 DEPs (116 upregulated, 94 downregulated) in the sotagliflozin vs LPS comparison, with 49 core overlapping DEPs that were dysregulated by LPS and normalized by sotagliflozin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that LPS challenge predominantly disrupted pathways, including extracellular matrix organization and the PI3K-Akt signaling cascade, which were targeted and restored by sotagliflozin. Functional validation demonstrated that sotagliflozin mitigated LPS-induced cardiomyocyte injury in a dose-dependent manner: it significantly improved cell viability (20 and 30 μM groups, P<0.01 and P<0.001, respectively), reduced lactate dehydrogenase (LDH) release (P<0.05 and P<0.001), and restored the antioxidant defense markers glutathione (GSH) and superoxide dismutase (SOD) (P<0.01 and P<0.001). Sotagliflozin also markedly downregulated mRNA levels of pro-inflammatory cytokines IL6, TNF, and NLRP3 (P<0.05 and P<0.01), and dose-dependently inhibited the aberrant upregulation of NLRP3 inflammasome activation markers NLRP3, cleaved Caspase-1, and cleaved IL-1β (30 μM group, P < 0.05), a regulatory effect further validated by immunofluorescence staining (P < 0.01). Additionally, sotagliflozin significantly ameliorated LPS-induced mitochondrial membrane potential collapse in cardiomyocytes (30 μM group, P<0.01). DISCUSSION: SRMI is a major driver of adverse clinical outcomes in patients with sepsis, yet no disease-modifying targeted therapies have been successfully translated into clinical practice to date. Here, we present the first unbiased proteomic profiling of the cardioprotective effects of sotagliflozin, a dual SGLT1/2 inhibitor, in lipopolysaccharide (LPS)-injured cardiomyocytes, addressing a critical unmet need in defining its repurposing potential for SRMI. Our data demonstrate that sotagliflozin exerts concentration-dependent protective effects against LPS-induced cardiomyocyte injury, characterized by mitigated oxidative stress, suppressed inflammatory responses (including inhibition of NLRP3 inflammasome activation at high concentrations), and preserved mitochondrial function. At the molecular level, sotagliflozin reverses LPS-induced proteomic dysregulation in cardiomyocytes, with the PI3K-Akt signaling cascade and ECM homeostasis identified as its two core regulatory axes. Dysregulation of the prosurvival, anti-inflammatory, and antioxidant PI3K-Akt pathway is closely associated with concurrent amelioration of multiple SRMI-related pathological phenotypes, from reduced cell death to preserved mitochondrial function. We further identify ECM organization as a previously unrecognized, exploratory regulatory target of sotagliflozin in SRMI, extending our understanding of its cardioprotective actions beyond its well-characterized metabolic effects. The 49 core DEPs whose LPS-induced dysregulation is reversed by sotagliflozin, identified herein, not only delineate the molecular basis of its protective effects but also represent promising novel candidate targets for SRMI gene therapy. The precise causal regulatory mechanisms underpinning these effects remain to be validated in future in vivo studies and functional genomic experiments. CONCLUSION: Sotagliflozin exerts cardioprotective effects against LPS-induced myocardial injury in H9C2 cardiomyocytes. This protection is mediated by the regulation of 49 core DEPs and key signaling pathways, most notably the PI3K/Akt pathway, which in turn attenuates excessive inflammatory responses, restores cellular redox balance, and ameliorates mitochondrial dysfunction.
Genome Editing Technologies for Cancer Therapy.
Chengizkhan G, Rajavelu A, Muthusami S … +6 more , Ganapathy V, Pathak S, Ramalingam S, Queimado L, Ramachandran I, Kumaran RI
Curr Gene Ther · 2026 Apr · PMID 42059213 · Publisher ↗
Cancer remains one of the leading causes of death worldwide, and the limitations of conventional therapies such as surgery, chemotherapy, and radiotherapy underscore the urgent need for innovative therapeutic strategies....
Cancer remains one of the leading causes of death worldwide, and the limitations of conventional therapies such as surgery, chemotherapy, and radiotherapy underscore the urgent need for innovative therapeutic strategies. While advances in early detection and treatment have improved outcomes in some regions, challenges such as micrometastasis, tumor relapse, and multidrug resistance continue to hinder long-term success. The multifactorial nature of cancer-driven by complex genetic mutations, diverse tumor microenvironments, and adaptive cancer cell behavior- demands more precise and effective solutions. Recent breakthroughs in molecular biology and genetic engineering have led to the emergence of genome editing technologies that offer promising avenues for targeted cancer therapy. This review highlights the evolution and application of key genome editing platforms, including meganucleases, zinc finger nucleases (ZFNs), transcription activator- like effector nucleases (TALENs), and the CRISPR/CAS9 system. Meganucleases were among the earliest tools with site-specific cutting ability, but limited versatility. ZFNs and TALENs offered greater modularity and target specificity through protein-DNA interactions. The CRISPR/CAS9 system revolutionized genome editing with its RNA-guided targeting, allowing for higher efficiency, simplicity, and flexibility in gene modification. These tools have enabled researchers to disrupt oncogenes, repair tumor suppressor genes, and manipulate signalling pathways involved in tumor progression, resistance, and metastasis. Moreover, ongoing advancements in delivery systems and gene repair mechanisms have further enhanced their therapeutic potential. We also discuss their translational potential from bench to bedside and explore future perspectives on how these technologies may revolutionize precision oncology, ultimately contributing to more effective treatment outcomes.
SPTSSA in Head and Neck Squamous Cell Carcinoma: Prognostic Significance and Implications for Gene- and Cell-Based Therapy.
Zhang Z, Zhang W, Tang M … +6 more , Chen Q, Xu X, Wei Y, Qian H, Wu H, Han L
Curr Gene Ther · 2026 Apr · PMID 42051093 · Publisher ↗
OBJECTIVE: The Tumor Microenvironment (TME) exerts a pivotal regulatory effect on the initiation, progression, and therapeutic response of Head and Neck Squamous Cell Carcinoma (HNSCC). Serine Palmitoyltransferase Small...
OBJECTIVE: The Tumor Microenvironment (TME) exerts a pivotal regulatory effect on the initiation, progression, and therapeutic response of Head and Neck Squamous Cell Carcinoma (HNSCC). Serine Palmitoyltransferase Small Subunit A (SPTSSA) is a TME-associated gene with well-characterized roles in multiple malignancies, yet its biological function and clinical significance in HNSCC remain largely elusive. This study aimed to systematically investigate the clinical value of SPTSSA in HNSCC and explore its potential as a novel prognostic biomarker and therapeutic target for this disease. METHODS: The expression of SPTSSA between Head and Neck Squamous Cell Carcinoma (HNSCC) tissues and non-tumoral tissues was compared using gene expression data. Associations with clinicopathologic features and patient outcomes were also analyzed. In vitro assays in HNSCC cell lines were used to test the effects of SPTSSA on malignant phenotypes. Multiplex immunofluorescence histochemistry was applied to assess SPTSSA protein levels in the TME and their relationship with immune markers and clinical factors. Circulating SPTSSA protein levels were measured in the blood of HNSCC patients to evaluate diagnostic value. RESULTS: SPTSSA expression was significantly higher in HNSCC tissues than in non‑tumoral tissues. Overexpression of SPTSSA enhanced HNSCC cell proliferation in vitro, supporting a pro‑tumorigenic function. Elevated SPTSSA protein levels in patient blood suggested potential diagnostic utility. In tumor tissues, SPTSSA protein expression correlated with CD4+ T cells, CD8+ T cells, and CD56+ natural killer cells, indicating a link with immune remodeling in the TME. High SPTSSA expression and advanced TNM stage independently predicted poor clinical outcomes. DISCUSSION: The study's findings establish SPTSSA as a critical oncogenic driver in HNSCC, with its upregulation closely linked to TME immune remodeling and poor patient prognosis. These results expand the oncogenic landscape of HNSCC and align with SPTSSA's pro-tumorigenic roles in other malignancies. Elevated circulating SPTSSA offers a non-invasive diagnostic tool for early detection, while its correlation with immune cell infiltration positions SPTSSA as a promising molecular target for HNSCC immunotherapy. CONCLUSION: SPTSSA is an oncogenic gene that drives HNSCC progression and is closely associated with an unfavorable patient prognosis. Its aberrant expression in both tumor tissues and peripheral blood may facilitate risk stratification and early clinical detection of HNSCC. Furthermore, the correlation between SPTSSA and immune cell infiltration in the TME highlights its potential as a promising molecular target for gene- and cell-based immunotherapeutic strategies in HNSCC.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe