Translational Oncology[JOURNAL]
Sun
200 papers
Inhibition of PTCH1 drug efflux activity enhances chemotherapy efficacy against triple negative breast cancers.
Cogoluegnes S, Kovachka S, Dubois T … +7 more , Würth R, Donato E, Trumpp A, Franco M, Luton F, Azoulay S, Mus-Veteau I
Transl Oncol · 2026 Jun · PMID 42001685 · Full text
Our previous work has revealed that PTCH1, a Hedgehog receptor which is expressed in many aggressive cancers, plays a role in transporting chemotherapeutic drugs out of cancer cells and contributes to their resistance to...
Our previous work has revealed that PTCH1, a Hedgehog receptor which is expressed in many aggressive cancers, plays a role in transporting chemotherapeutic drugs out of cancer cells and contributes to their resistance to chemotherapy. PTCH1 transports drugs via the proton motive force using the 'reverse pH gradient', which makes its drug efflux activity specific to cancer cells and PTCH1 a highly relevant and specific new therapeutic target for cancer treatment. We have identified a small molecule produced by a marine sponge as being able to inhibit PTCH1 efflux activity and increase the efficacy of vemurafenib treatment on BRAF-mutated melanoma cells in vitro and in vivo in mice. In the present study, we demonstrate the presence of PTCH1 mRNA in tumour samples and circulating tumour cells from breast cancer patients, particularly those with triple-negative breast cancer (TNBC). TNBC is the most aggressive breast cancer subtype, characterised by a high risk of resistance to chemotherapy and a high potential for relapse. Our analyses reveal that high levels of PTCH1 mRNA are associated with a poor prognosis in TNBC patients. We found that inhibiting PTCH1 drug efflux activity significantly increased the cytotoxic effect of chemotherapies such as doxorubicin and docetaxel in three TNBC cell lines. Overall, our findings suggest that PTCH1 plays a role in the resistance of TNBC cells to chemotherapy, and that using a PTCH1 efflux inhibitor during neoadjuvant or adjuvant therapy could enhance the efficacy of treatment against PTCH1-expressing TNBC, while preventing treatment resistance, relapse, and metastasis formation.
AAA ATPase TRIP13 is overexpressed in prostate cancer and promotes tumor progression.
Afaq F, Pathi SS, Chakravarthi BVSK … +8 more , Chandrashekar DS, Carskadon S, Diffalha SA, Kunju LP, Palanisamy N, Manne U, Singh R, Varambally S
Transl Oncol · 2026 Jun · PMID 42000600 · Full text
Prostate cancer (PCa), a common malignancy, is a leading cause of cancer-related deaths among men. Advances in high-throughput technologies have led to the identification of various genetic alterations, including amplifi...
Prostate cancer (PCa), a common malignancy, is a leading cause of cancer-related deaths among men. Advances in high-throughput technologies have led to the identification of various genetic alterations, including amplifications, deletions, mutations, gene fusions, and aberrant gene expressions, associated with PCa initiation and progression. Identifying key drivers of tumor progression and their underlying signaling pathways contributes to early diagnosis and therapeutic targeting. Here, we showed that thyroid hormone receptor-interacting protein 13 (TRIP13), a member of the AAA-ATPase family is overexpressed in PCa. Additionally, we observed amplification of the TRIP13 locus in a small subset of PCa samples. Functional studies demonstrated that TRIP13 knockdown in PCa cells reduced their proliferation and invasion. Furthermore, ectopic overexpression of TRIP13 in prostate epithelial cells (RWPE-1) resulted in enhanced cell invasion. Additionally, pharmacologic inhibition of TRIP13 by the small molecule inhibitor DCZ0415 suppressed PCa cell proliferation, induced apoptosis, modulated markers of the epithelial-mesenchymal transition (EMT), and inhibited tumor growth. Overall, these findings highlight a functional role for TRIP13 in PCa progression and demonstrate its potential as a therapeutic target in TRIP13-overexpressing PCa.
Corrigendum to "Androgen receptor may promote tumor progression via TTF-1/EGFR pathway in metastatic nasopharyngeal carcinoma" [Translational Oncology, Volume 65, March 2026, 102670].
Lin CY, Huang CY, Lui KW … +15 more , Chao YK, Yeh CN, Lee LY, Huang Y, Yang Z, Hsieh CH, Fan HC, Lin AC, Chang KP, Lin CY, Wang HM, Chao M, Chang YS, Li HP, Hsu CL
Transl Oncol · 2026 May · PMID 42000368 · Full text
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Corrigendum to " Computed tomography- and magnetic resonance imaging-based multi-modality radiomics models for predicting survival in esophageal cancer patients" [Translational Oncology 65 (2026) 102686].
Chu F, Li D, Wang Z … +6 more , Bai B, Zhao K, Wang S, Wang C, Yang G, Qu J
Transl Oncol · 2026 May · PMID 42000367 · Full text
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Transcriptomic and single-cell analyses reveal the prognostic value of ETV4 and its role in shaping the immune landscape of colorectal cancer.
Meng R, Wang S, She Z … +7 more , Wang H, Wu B, Qiao Y, Chen P, Nargerel, Yang X, Wang L
Transl Oncol · 2026 Jun · PMID 41997046 · Full text
BACKGROUND: Colorectal cancer (CRC) remains a major health threat with poor prognosis in advanced stages. The transcription factor ETV4 (ETS translocation variant 4) has been implicated in various cancers, but its specif...
BACKGROUND: Colorectal cancer (CRC) remains a major health threat with poor prognosis in advanced stages. The transcription factor ETV4 (ETS translocation variant 4) has been implicated in various cancers, but its specific role, prognostic value, and mechanisms in CRC, particularly concerning the tumor immune microenvironment, are not fully understood. METHODS: We performed a comprehensive analysis using transcriptomic data from The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing data from the GEO database (GSE231559). Bioinformatic approaches included survival analysis, immune cell infiltration estimation via CIBERSORT, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and single-cell clustering. Experimental validation was conducted on clinical CRC tissue samples and HCT-116 cells, employing flow cytometry, immunohistochemistry, quantitative real-time PCR (Q-PCR), and Western blot. RESULTS: In the TCGA cohort, ETV4 was significantly upregulated in 650 CRC tissues vs 51 adjacent normal tissues, with high expression linked to poorer overall survival in CRC patients.Immune infiltration analysis revealed correlations between ETV4 expression and specific immune cell subsets, notably macrophages. Flow cytometry and immunohistochemistry confirmed that high ETV4 expression was linked to increased polarization of immunosuppressive M2-type macrophages in the tumor microenvironment. Furthermore, bioinformatic GSVA and subsequent wet-lab experiments demonstrated that ETV4 is a downstream target gene of the WNT/β-catenin signaling pathway. Activation of this pathway upregulated ETV4 expression, while inhibition downregulated it, establishing a functional link. CONCLUSION: This integrative study reveals that ETV4 is a prognostic biomarker in CRC. It promotes tumor progression by reshaping the immunosuppressive microenvironment, particularly through inducing M2 macrophage polarization, and is regulated by the oncogenic WNT/β-catenin pathway. These findings suggest that ETV4 is expected to become a potential diagnostic biomarker and candidate therapeutic target for colorectal cancer, providing a novel direction for subsequent research on the diagnosis and treatment of CRC.
CD3 and PD-L1 tissue expression have synergistic value in head and neck squamous cell carcinoma prognosis.
Witzleben AV, Remark R, Idel C … +15 more , Ribbat-Idel J, Krupar R, Schröck A, Klümper N, Doescher J, Sikora AG, Kors TA, Vahl JM, Brand M, Sonntag M, Brunner C, Hoffmann TK, Perner S, Gnjatic S, Laban S
Transl Oncol · 2026 Jun · PMID 41997045 · Full text
INTRODUCTION: T cell infiltrates, particularly CD3 T cells, have been linked to a favorable prognosis in cancer. However, the influence of PD-L1 expression on survival remains controversial, particularly in patients who...
INTRODUCTION: T cell infiltrates, particularly CD3 T cells, have been linked to a favorable prognosis in cancer. However, the influence of PD-L1 expression on survival remains controversial, particularly in patients who do not receive immune checkpoint inhibition. This goal of this study was to combine CD3 density and PD-L1 expression to assess their individual and combined prognostic value in head and neck squamous cell carcinoma (HNSCC) patients treated with surgery and adjuvant therapy. MATERIALS AND METHODS: A tissue microarray of 458 HNSCC primary tumor samples was analyzed for CD3 and PD-L1 expression using multiplex immunohistochemistry. CD3 densities were quantified using digital image analysis (QuPath), and PD-L1 expression was categorized by the Combined Positive Score (CPS). Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared across different expression profiles using the Kaplan-Meier method followed by a multivariate cox regression analysis. RESULTS: CD3 tumors (defined as greater the median CD3 expression) were associated with longer OS and RFS compared to CD3 tumors (below median). Similarly, PD-L1 expression at CPS ≥ 1 was linked to significantly better survival outcomes than CPS < 1. The combination of CD3 and PD-L1 CPS ≥ 1 showed the most favorable prognosis. CONCLUSION: The combined assessment of CD3 density and PD-L1 expression outperforms either marker alone in predicting survival outcomes in surgically treated patients without immunotherapy. CD3 and PD-L1 CPS ≥ 1 identifies patients with favorable prognosis and response to standard-of-care treatment. Nonetheless, the potential relevance of these markers for guiding immunotherapy in other setting remains to be explored.
Clinical usefulness of polygenic risk scores in risk prediction models for lung cancer screening and lung nodule management.
Boumtje V, Li Z, Gaudreault N … +9 more , Saavedra Armero V, Boudreau DK, Plante S, Biardel S, Eslami A, Martel S, Thériault S, Joubert P, Bossé Y
Transl Oncol · 2026 Jun · PMID 41990546 · Full text
BACKGROUND: Lung cancer mortality decreases as a result of low-dose computed tomography (LDCT) screening, but suffers from low uptake and high false-positive rates. The impact of integrating genetic risk using a polygeni...
BACKGROUND: Lung cancer mortality decreases as a result of low-dose computed tomography (LDCT) screening, but suffers from low uptake and high false-positive rates. The impact of integrating genetic risk using a polygenic risk score (PRS) to optimize lung cancer screening remains underexplored. METHODS: We developed a genome-wide PRS and evaluated its performance in pre- and post-screening contexts. Screening eligibility was assessed using two UK Biobank (UKB) subsets: UKB (n = 8957; PLCOm2012norace risk ≥2%) and UKB (n = 74,024 meeting screening eligibility criteria). To evaluate nodule management, we used a cohort of 669 ever-smokers with PLCO ≥2% and Lung-RADS score ≥3, referred to as SYNERGIQC. Multivariable Cox models, time-dependent area under the curve (AUC), and decision curve analyses (DCA) evaluated association, discrimination, and clinical net benefit. RESULTS: In UKB, the PRS was associated with a hazard ratio (HR) of 1.18 per standard deviation. In UKB, PRS showed HR of 1.34. Adding PRS to the PLCOm2012 model improved discrimination (AUC: 0.707 vs 0.696; P = 6.85e[likelihood ratio test]) and correctly reclassified 9.2% of incident lung cancer cases. Six-year absolute risks stratified by PRS deciles indicate 3.1-fold increase in the top compared to the bottom decile. In SYNERGIQC, HR was 1.22. In this context, DCA indicated a modest net benefit for decision thresholds between 10% and 30%. CONCLUSION: PRS in lung cancer reveals context-dependent net benefit across studied populations. Although PRS adds limited value for determining screening eligibility, it may help reclassify borderline individuals and inform decisions regarding closer follow-up or invasive diagnostic procedures for high-risk screened groups.
Integrated spatial and single‑cell transcriptomics maps disulfidptosis in renal cell carcinoma and reveals PDLIM1 as a prognostic biomarker and potential therapeutic target.
Liu W, Liu X, Yi J … +13 more , Tang Z, Dai Z, Song J, Chen T, Wang J, Wang J, Jiang W, Jiang A, Wu Z, Tang L, Jin Y, Chen Y, Wang L
Transl Oncol · 2026 Jun · PMID 41985321 · Full text
BACKGROUND: Disulfidptosis is a regulated cell death program linked to redox stress, metabolism, and the actin cytoskeleton. Its organization in tissue and clinical relevance in renal cell carcinoma are not well defined....
BACKGROUND: Disulfidptosis is a regulated cell death program linked to redox stress, metabolism, and the actin cytoskeleton. Its organization in tissue and clinical relevance in renal cell carcinoma are not well defined. METHODS: We integrated spatial transcriptomics from six renal cancer sections with four single cell RNA sequencing cohorts. Disulfidptosis scores were computed, RCTD deconvolution and epithelial reclustering were used to localize subpopulations, and pathway enrichment and CytoTRACE assessed metabolism and stemness. External validation used TCGA-KIRC, KIRP and additional public datasets. Candidate genes were nominated by intersecting disulfidptosis, Cluster 3, and Epi_C5 signatures. PDLIM1 function was tested by sh-RNA in renal cancer cell lines with qPCR, proliferation, wound healing, and Transwell assays. RESULTS: Disulfidptosis showed strong intra heterogeneity. Spatial clusters 2, 3, and 6 were enriched, with Cluster 3 higher in tumors and linked to worse survival, and Cluster 6 context dependent yet adverse. Signals localized mainly to epithelial cells. Epithelial reclustering identified Epi_C5 with the highest disulfidptosis and Cluster 3 scores. Disulfidptosis-high cells were enriched for N glycan biosynthesis, purine and pyrimidine metabolism, oxidative phosphorylation, and nitrogen metabolism, with spatial overlap between nitrogen metabolism and disulfidptosis. Epi_C5 upregulated extracellular matrix programs, showed higher CytoTRACE, and associated with poor prognosis in both TCGA cohorts. Intersecting signatures nominated PDLIM1, which was tumor elevated and correlated with Epi_C5 and CytoTRACE. PDLIM1 knockdown reduced proliferation, and migration. CONCLUSIONS: We define a disulfidptosis‑associated epithelial malignant state in renal cancer and nominate PDLIM1 as a candidate node for patient stratification and therapeutic development.
Identification of MYC co-expression gene: POLR3G is associated with cell senescence, immunotherapy, chemotherapy responses, and clinical prognosis in bladder cancer patients.
Zhu L, Liu Y, Lan J … +5 more , Cai E, Sun D, Liu J, Zong L, Cong Z
Transl Oncol · 2026 Jun · PMID 41985320 · Full text
BACKGROUND: The MYC oncogene is a central driver of bladder cancer (BLCA) pathogenesis. However, the systematic role of its co-expressed gene network in BLCA progression, tumor microenvironment remodeling, and therapeuti...
BACKGROUND: The MYC oncogene is a central driver of bladder cancer (BLCA) pathogenesis. However, the systematic role of its co-expressed gene network in BLCA progression, tumor microenvironment remodeling, and therapeutic response remains largely unexplored. METHODS: Using the TCGA-BLCA dataset, we identified MYC co-expressed genes via the LinkedOmics platform. Consensus clustering was employed to define molecular subtypes based on this network. A prognostic signature was constructed using LASSO Cox regression. Immune infiltration was assessed with the xCell and TIP algorithms, and therapy responses were predicted via TIDE and drug sensitivity analysis. POLR3G's expression was validated in clinical samples using immunohistochemistry. RESULTS: Consensus clustering stratified BLCA patients into two distinct subtypes with significant survival differences, linked to NF-κB/IL-17/JAK-STAT and PPAR signaling pathways, respectively. A robust five-gene prognostic signature was developed. The high-risk group, characterized by an immunosuppressive microenvironment and elevated immune checkpoint expression, demonstrated poorer survival and predicted resistance to immune checkpoint blockade. Among the signature genes, POLR3G emerged as the most powerful independent prognostic factor. Furthermore, POLR3G expression was correlated with resistance to both chemotherapy and immunotherapy. Its upregulation in BLCA tissues was confirmed experimentally. CONCLUSION: Our study reveals that the MYC co-expression network is critical for BLCA heterogeneity. We established a novel prognostic signature with significant clinical utility for risk stratification and therapy guidance. POLR3G is highlighted as a pivotal oncogene associated with BLCA cell senescence and treatment resistance, thereby representing a promising new biomarker and therapeutic target.
STC2-mediated calcium homeostasis dysregulation in the osteosarcoma microenvironment: Insights from single-cell sequencing and machine learning.
Yao K, Jiawei Q, Jietao X … +4 more , Xijun W, Hong Z, Qing B, Jun L
Transl Oncol · 2026 Jun · PMID 41985319 · Full text
BACKGROUND: Osteosarcoma (OS) is an aggressive bone malignancy with a poor prognosis. Dysregulated calcium homeostasis may contribute to OS progression. METHODS: Various machine learning algorithms were integrated into m...
BACKGROUND: Osteosarcoma (OS) is an aggressive bone malignancy with a poor prognosis. Dysregulated calcium homeostasis may contribute to OS progression. METHODS: Various machine learning algorithms were integrated into multiple model combinations to identify key prognostic genes. Single-cell expression profiling was conducted to assess STC2 expression across different cell types within the OS microenvironment. Experimental validation was performed in OS cell lines (U2OS and 143B) using lentiviral shRNA-mediated knockdown, qPCR, proliferation assays, and migration/invasion assays. Immune infiltration and potential immunotherapy response were further explored using immune deconvolution, immune checkpoint analysis, TIDE, and SubMap. RESULTS: Calcium homeostasis-related dysregulation was associated with osteosarcoma progression, and machine-learning analysis identified STC2 as the most important prognostic gene. Single-cell analysis revealed that STC2 was predominantly expressed in endothelial, fibroblast, and malignant cells. In vitro experiments showed that knockdown of STC2 in OS cells significantly inhibited cell proliferation, migration, and invasion. Specifically, CCK-8, colony formation, and EdU assays demonstrated decreased cell proliferation, while Transwell assays revealed reduced migratory and invasive capacities of STC2-knockdown OS cells. Moreover, TIDE and SubMap analyses suggested that low STC2 expression was computationally associated with a higher predicted likelihood of response to immune checkpoint inhibitors. CONCLUSIONS: Our findings suggest that calcium homeostasis dysregulation is involved in OS progression and that STC2 is a prioritized prognostic and functional candidate within this network. The findings suggest that STC2 may serve as a potential therapeutic target and candidate biomarker for OS, including in the context of predicted immunotherapy response, although this requires further validation.
PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.
Li J, Mu D, Li J … +4 more , Lan M, Wu W, Zhang S, Dai Y
Transl Oncol · 2026 Jun · PMID 41967334 · Full text
Poly-ADP-ribose polymerase (PARP) is a multifunctional ribozyme that is involved in a variety of biological functions, including DNA repair, modulation of chromatin structure, RNA transcription, cell division, metabolism...
Poly-ADP-ribose polymerase (PARP) is a multifunctional ribozyme that is involved in a variety of biological functions, including DNA repair, modulation of chromatin structure, RNA transcription, cell division, metabolism, mitochondrial biology, oxidative stress biology, and cell death and differentiation. PARP inhibitors (PARPi) are a new class of targeted drugs widely used in the treatment of cancer with BRCA1/2 mutations and non-malignant diseases. Although PARPi has been known to affect the energy metabolism of cells, its exact effects and mechanisms on this process have not yet been fully understood. In this review article, we aim to provide a comprehensive overview of the current understanding of PARPi's effects on various physiological processes involving cellular energy metabolism, highlighting the importance of further exploring how the human body maintains the balance of energy metabolism during PARPi therapy. We also highlight the importance of future studies on the relationship between PARPi treatment and the depletion of NAD+ levels, the activation of PARP1, or the transition between different patterns of energy metabolism, to provide more insights into the safety and efficacy of PARPi in clinical practice.
Chemotherapy with bevacizumab and pembrolizumab followed by radiotherapy for unclassified round cell sarcomas of the gallbladder: A case report and review of literature.
Wang D, Li T, Wang X … +5 more , Wang Y, Xu G, Xiao X, Hu L, Xu C
Transl Oncol · 2026 May · PMID 41956009 · Full text
Unclassified round cell sarcomas (URCS) are a rare sarcoma subtype. Systemic treatment options for advanced URCS are limited, primarily consisting of radiotherapy and chemotherapy, while the efficacy and prerequisites fo...
Unclassified round cell sarcomas (URCS) are a rare sarcoma subtype. Systemic treatment options for advanced URCS are limited, primarily consisting of radiotherapy and chemotherapy, while the efficacy and prerequisites for immunotherapy in URCS remain unclear. A better understanding of factors influencing the response to immunotherapy in URCS may facilitate the development of combination treatment strategies to prolong patient survival. This study reports a 60-year-old male patient with gallbladder URCS who was administered a combination of chemotherapy, bevacizumab, and pembrolizumab, followed by radiotherapy, achieving a progression-free survival of 11 months. This result supports the potential application of immunotherapy in advanced URCS. The patient exhibited vascular endothelial growth factor receptor amplification, mutations in CHEK1, ERCC3, and TP53, deletion of CD274 (gene of PD-L1), and microsatellite stability. These findings suggest that immunotherapy may be beneficial to URCS patients with low PD-L1 expression and microsatellite stability, when accompanied by immunotherapy-associated genetic alterations.
NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.
Yang P, Li X, Yang L … +4 more , Xiao N, Ren L, Ji M, Yang H
Transl Oncol · 2026 May · PMID 41956008 · Full text
Hepatocellular carcinoma (HCC) develops predominantly in the context of chronic liver inflammation and remains a leading cause of cancer-related mortality worldwide. Increasing evidence indicates that nuclear factor-κB (...
Hepatocellular carcinoma (HCC) develops predominantly in the context of chronic liver inflammation and remains a leading cause of cancer-related mortality worldwide. Increasing evidence indicates that nuclear factor-κB (NF-κB) signaling plays a central role in linking inflammatory stress to malignant progression in HCC. Beyond transient inflammatory activation, NF-κB is pathologically stabilized through alterations in proteostasis, kinase signaling, and loss of endogenous inhibitory circuits, resulting in sustained transcriptional activity. This persistent NF-κB signaling orchestrates multiple adaptive programs that collectively drive tumor growth, metabolic reprogramming, immune evasion, and resistance to therapy. In particular, NF-κB integrates proliferative and survival signaling with glycolytic dependence, redox homeostasis, epithelial-mesenchymal transition, and immunosuppressive remodeling of the tumor microenvironment. Moreover, NF-κB functions as a shared survival hub under therapeutic stress, promoting resistance to radiotherapy, chemotherapy, and ferroptosis-inducing strategies. Importantly, emerging evidence highlights the role of non-coding RNAs and tumor suppressors as endogenous brakes that restrain NF-κB activity, whose disruption contributes to its pathological fixation in HCC. In this review, we synthesize recent mechanistic and translational advances that redefine NF-κB as a central adaptive program in hepatocellular carcinoma. We further discuss the clinical implications of NF-κB signaling for tumor stratification and therapeutic intervention, emphasizing that effective targeting of HCC may require selective disruption of NF-κB-dependent adaptive modules rather than global pathway inhibition.
Integrative analysis of urinary microRNAs for prostate cancer detection: A proof-of-concept study.
Samani LA, Rahmani S, Kashi AH … +2 more , Ziaee SAM, Mowla SJ
Transl Oncol · 2026 May · PMID 41950670 · Full text
BACKGROUND: Liquid biopsies analyzing circulating nucleic acids offer a non‑invasive strategy for early detection, disease monitoring, and precision medicine. Among these, urinary microRNAs (miRNAs) have emerged as robus...
BACKGROUND: Liquid biopsies analyzing circulating nucleic acids offer a non‑invasive strategy for early detection, disease monitoring, and precision medicine. Among these, urinary microRNAs (miRNAs) have emerged as robust biomarkers owing to their stability and regulatory effects on gene expression and tumor progression. METHODS: A multi‑omics integrative analysis combining public microarray, bulk RNA‑seq, and single‑cell RNA‑seq datasets was performed to identify miRNAs differentially expressed between prostate cancer (PCa) patients and healthy controls. The diagnostic potential of these candidates was assessed using receiver operating characteristic (ROC) analysis and support vector machine (SVM) modeling. Validation was conducted through quantitative polymerase chain reaction (qPCR) on urine samples from 19 PCa and 7 benign prostatic hyperplasia (BPH) subjects. RESULTS: miR-23b-3p demonstrated consistent downregulation across transcriptomic datasets derived from urine, serum, and tissue. ROC and SVM analyses indicated strong diagnostic performance. Urinary qPCR validation yielded an area under the curve (AUC) of 0.79 (95% CI: 0.51-1.00), sensitivity of 0.73 (95% CI: 0.39-0.94), and specificity of 0.86 (95% CI: 0.42-1.00). CONCLUSIONS: The findings suggest that miR-23b-3p represents a promising complementary biomarker for non‑invasive PCa diagnosis. Further large‑scale validation integrating transcriptomic and clinical data is warranted to confirm its clinical applicability.
Single-cell transcriptomic analysis reveals that the circRNA circGCLM promotes tumorigenesis and confers cisplatin resistance in NSCLC through the miR-505-3p/ERBB4 axis.
Ma Y, Huang B, Wang H … +6 more , Xue M, Liu Y, Jin Y, Wang C, Gu S, Zhou Y
Transl Oncol · 2026 May · PMID 41950669 · Full text
BACKGROUND: The circular RNAs (circRNAs) have been implicated in chemoresistance, yet the specific roles of individual circRNAs in non-small cell lung cancer (NSCLC) remain largely unexplored. Here, we identified circGCL...
BACKGROUND: The circular RNAs (circRNAs) have been implicated in chemoresistance, yet the specific roles of individual circRNAs in non-small cell lung cancer (NSCLC) remain largely unexplored. Here, we identified circGCLM as a novel driver of NSCLC tumorigenesis and cisplatin (DDP) resistance, and investigated its molecular mechanism of action. METHODS: CircGCLM expression was examined in DDP-resistant and parental NSCLC cells. Loss-of-function studies were conducted to evaluate the effects on cell proliferation, apoptosis, and DDP sensitivity. The circGCLM/miR-505-3p/ERBB4 axis was validated using dual-luciferase reporter assays, RNA immunoprecipitation (RIP), and rescue experiments. ERBB4 expression dynamics was uncovered by single-cell transcriptomic analysis. RESULTS: CircGCLM was markedly upregulated in DDP-resistant NSCLC cells compared to their parental cells. Functional loss-of-function studies demonstrated that circGCLM knockdown suppressed proliferation, restored DDP sensitivity, and promoted apoptosis in these resistant cells. Mechanistically, circGCLM acted as a competitive endogenous RNA (ceRNA) for microRNA-505-3p (miR-505-3p), which led to the derepression and consequent upregulation of its target, erb-b2 receptor tyrosine kinase 4 (ERBB4). Thus, the oncogenic functions of circGCLM, including the promotion of DDP resistance and other malignant phenotypes, were mediated through the miR-505-3p/ERBB4 axis. CONCLUSIONS: In summary, our findings established that circGCLM contributed to DDP resistance in NSCLC, at least in part, by sponging miR-505-3p to derepress ERBB4, highlighting a potential therapeutic target for overcoming chemoresistance.
Circulating low-density neutrophils as biomarkers of resistance to first-line anti-PD-1/PD-L1 immunotherapy in non-small cell lung cancer.
Castro N, Labiano I, Martínez-Aguillo M … +17 more , Huerta AE, Morilla I, Teijeira L, Serrano D, Caseda I, Lecumberri A, Amat I, Zuazo M, Chocarro L, Blanco E, Escors D, Kochan G, Fernández Irigoyen J, Vera R, Calvo A, Alsina M, Arasanz H
Transl Oncol · 2026 May · PMID 41950668 · Full text
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC), however reliable predictive biomarkers are lacking. Our group previously reported an association betw...
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC), however reliable predictive biomarkers are lacking. Our group previously reported an association between high levels of circulating low-density neutrophils (LDNs) and resistance to ICI monotherapy. We present updated results, including a validation cohort, proteomic characterization of LDNs, and in vivo experiments exploring mechanisms of resistance. METHODS: NSCLC patients treated with first line ICI monotherapy (n=60) or combined with chemotherapy (CT+ICI) (n=60) were recruited. LDNs were quantified by flow cytometry and correlated with clinical outcomes. Phenotypes of LDNs and conventional neutrophils were characterised by flow cytometry and quantitative proteomics. Plasma cytokine measurements and in vivo experiments were conducted to assess the role of LDNs in ICI resistance. RESULTS: High baseline LDN levels were significantly associated with primary resistance to ICI monotherapy, with patients showing an overall response rate (ORR) of 17% vs 50% (p=0.04) and median progression free survival (mPFS) of 2.3 months vs 21.8 months (p < 0.001). No such association was seen in patients treated with CT+ICI, showing a LDN depletion in responders. LDNs exhibited an aged phenotype and distinct proteomic profile. Plasma from high-LDN patients showed elevated myeloid-expansion (M-CSF, IL1β) and inflammatory cytokines (CXCL9, IL-25). Depletion of Gr1+ population enhanced response to ICI and CT+ICI in the Lewis Lung Carcinoma (LLC) model with high LDNs. CONCLUSION: High baseline LDNs predict resistance to ICI monotherapy in NSCLC and combination with chemotherapy may overcome this resistance. Additional therapeutic strategies targeting LDNs could enhance immunotherapy efficacy.
Single-cell transcriptome analysis indicated that immune-related programmed cell death modification features could predict the clinical outcomes of patients with ovarian cancer.
Sun J, Jing L, Zhu X … +4 more , Yang H, Sun Y, Lu X, Liu Z
Transl Oncol · 2026 May · PMID 41946148 · Full text
BACKGROUND: Ovarian cancer (OV) is characterized by the highest mortality rate among gynecological malignancies. Suboptimal early diagnosis and ineffective prognostic prediction of OV contribute to poor survival outcomes...
BACKGROUND: Ovarian cancer (OV) is characterized by the highest mortality rate among gynecological malignancies. Suboptimal early diagnosis and ineffective prognostic prediction of OV contribute to poor survival outcomes for most patients. This study aimed to identify immune-related programmed cell death (IPCD) signatures and find the valuable biomarker for predicting OV prognosis. METHODS: All OV datasets were downloaded from public databases of TCGA, GEO and ICGC. Prognostic genes from IPCD-related differential genes were screened by univariate cox regression analysis. The construction of the IPCDS model was performed via 101 algorithm combinations. The prognostic performance of IPCDS model were examined by Kaplan-Meier analysis and timeROC curves. TIDE algorithm was used to predict the immune response of TCGA data. RESULTS: 88 IPCD-related prognostic genes were screened for modeling IPCDS. A significantly higher OS in low-IPCDS group was observed among most OV datasets than in high-IPCDS group. 2-, 3-, and 5-year timeROC results of each OV dataset revealed the excellent predictive value of IPCDS for OV, showing a relatively higher AUC after treated 2 years. The low IPCDS group had a higher TIDE value, while the no response group had a higher IPCDS value. In the pan-cancer immunotherapy dataset, patients in the low IPCDS group had a longer overall survival period and a significant immunotherapy effect. Besides, model gene PDGFRA were found to have predictive performance for OV. We validated the upregulation of PDGFRA and C-MYC in ovarian cancer tissues through Western blot and confirmed their co-localization and immunofluorescence analyses. CONCLUSION: Our study develops a novel prognostic model IPCDS for OV. IPCD-related gene PDGFRA serves as a prognosis factor play in predicting survival outcomes of OVs.
CD38 overexpression drives glioblastoma progression via L1CAM/ICAM1/JAK-STAT-Driven tumor microenvironment rewiring.
Norouzi S, Aulakh S
Transl Oncol · 2026 May · PMID 41946147 · Full text
BACKGROUND: Glioblastoma (GBM), a lethal primary brain malignancy, is characterized by dysregulated recruitment of tumor-associated macrophages and myeloid-derived suppressor cells, which promotes tumor growth, and enabl...
BACKGROUND: Glioblastoma (GBM), a lethal primary brain malignancy, is characterized by dysregulated recruitment of tumor-associated macrophages and myeloid-derived suppressor cells, which promotes tumor growth, and enables immune evasion. Given CD38's role as a multifunctional glycoprotein in hematological malignancies where it regulates immune cell trafficking, we hypothesized that CD38 overexpression in GBM modulates the tumor immune microenvironment. METHODS: We utilized the CRISPRa system to enhance CD38 expression in mouse syngeneic GL-261 cells. A murine GBM model was generated by intracranial injection of CD38-overexpressing (CD38-OE) GL-261 cells or CD38 wild-type (WT) or (parental)GL-261 cells into C57BL/6 mice. We utilized serial brain MRIs for tumor progression and assessed overall survival using Kaplan-Meier analysis. We performed multiplex flow cytometry and cytokine assays on brain tumor tissue. Data were analyzed using one-way ANOVA and unpaired t-tests. RESULTS: Median OS was significantly reduced in CD38-OE mice (26.5 days) versus CD38-WT (35.7 days; p < 0.0001; n = 11/group). Tumor size (in vivo) in CD38-OE vs CD38-WT at day 10 (8.44 mm³ vs. 2.16 mm³; p = 0.0004) and day 17 (34.75 mm³ vs. 8.51 mm³; p = 0.0048). Compared to CD38-WT, CD38-OE tumors showed increased infiltration of glioma-associated macrophages (GAMs) (8.43-fold increase; p < 0.0001), monocytic MDSCs (12.53-fold increase; p < 0.0002), polymorphonuclear MDSCs (15.66-fold increase; p < 0.0001), and T-regs (7.22-fold increase; p < 0.0001). Cytokine profiling indicated elevated CXCL10/IP-10, TIMP-1, and ICAM-1 in CD38-OE tumors. CONCLUSIONS: CD38 overexpression in GBM drives tumor progression by amplifying immunosuppressive TME remodeling, positioning CD38 as a compelling target for further clinical investigation, supported by preliminary efficacy of daratumumab (NCT04922723) in patients with GBM.
Proof-of-concept study of clinical use of blood-based MAVS biosensor in predicting immunotherapy response in SCLC patients.
Amato L, Tavoletta I, De Rosa C … +17 more , Seggio M, Arcadio F, Capaldo S, Ul Haq F, Tuccillo C, Esposito C, di Guida G, Iommelli F, De Rosa V, Reginelli A, Cappabianca S, Morgillo F, Ciardiello F, Nardone V, Cennamo N, Della Corte CM, Zeni L
Transl Oncol · 2026 May · PMID 41936750 · Full text
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with poor prognosis and limited benefit from immune checkpoint inhibitors (ICIs). Biomarker-driven patient stratification has been hindered by small bio...
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with poor prognosis and limited benefit from immune checkpoint inhibitors (ICIs). Biomarker-driven patient stratification has been hindered by small biopsy samples, high tumor heterogeneity, and the limited predictive value of PD-L1 and tumor mutation burden. Mitochondrial antiviral-signaling protein (MAVS) has emerged as a potential immune activation marker, particularly in patients receiving DNA-damaging therapies. We report a proof-of-concept clinical study evaluating a surface plasmon resonance-plastic optical fiber (SPR‑POF) biosensor functionalized with anti-MAVS antibodies to detect the protein in serum from SCLC patients undergoing chemo-immunotherapy, with or without radiotherapy. The biosensor achieved a limit of detection of 0.13 nM in human diluted serum and demonstrated high selectivity against common serum proteins. In a cohort stratified as best responders (disease control >6 months) and non-responders (progressive disease as best response), MAVS levels measured in responders were on average tenfold higher than in non-responders, consistent with previous preclinical PBMC and western blot data. The SPR‑POF platform demonstrated portability, cost-effectiveness (estimated 5 USD/unit), and operational simplicity, highlighting its potential for point-of-care testing (POCT) applications. Although limited by small patient numbers, these findings support MAVS as a promising predictive biomarker in SCLC, warranting validation in larger prospective studies.
CCL2: A double-edged sword in neuroblastoma, with a critical role in MYCN-amplified tumors.
Jannot L, Gazeu A, Bendriss-Vermare N … +2 more , Pochon C, Sartelet H
Transl Oncol · 2026 May · PMID 41936749 · Full text
Neuroblastoma (NB) is the most common extracranial solid tumor in children, characterized by significant clinical heterogeneity and immune evasion. MYCN oncogene amplification is a major driver of tumor aggressiveness an...
Neuroblastoma (NB) is the most common extracranial solid tumor in children, characterized by significant clinical heterogeneity and immune evasion. MYCN oncogene amplification is a major driver of tumor aggressiveness and poor prognosis and is inversely correlated with immune infiltration in the tumor microenvironment (TME). Emerging evidence highlights the pivotal role of the chemokine C-C motif ligand 2 (CCL2) in modulating the immune landscape of NB. CCL2 influences the recruitment of various immune cells, including invariant natural killer T (iNKT) cells, dendritic cells (DCs), monocytes, macrophages, and regulatory T cells (Tregs), thereby shaping either pro- or anti-tumor responses depending on the context. MYCN-amplified tumors display reduced CCL2 expression, resulting in limited immune cell recruitment and the establishment of a "cold" TME with poor immune surveillance. In contrast, non-amplified tumors exhibit higher levels of CCL2, which attracts both anti-tumor immune cells such as DCs and macrophages, as well as pro-tumor populations including Tregs and tumor-associated macrophages (TAMs). These observations underscore the dual and context-dependent role of CCL2 in NB pathogenesis. Therapeutically, targeting the CCL2/CCR2 axis has shown promise in preclinical models, including approaches to enhance CAR-T cell trafficking and reduce TAM-mediated immunosuppression. Overall, CCL2 emerges as a central immunomodulatory molecule in NB, tightly linked to MYCN status and the composition of the TME. Understanding its complex biology is critical for the development of novel immunotherapies aimed at restoring effective anti-tumor immune responses, particularly in high-risk MYCN-amplified NB. Targeting the CCL2 axis represents a promising strategy to improve NB patient outcomes.
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