Clinical & Translational Oncology[JOURNAL]
Sun
200 papers
OSBPL3 promotes LUAD metastasis and glycolysis through transcriptional upregulation of PLAU via NFE2L2.
Zhang Q, Zhang J, Li J … +4 more , Chen S, Liu Y, Li K, Guo M
Transl Oncol · 2026 Apr · PMID 41687403 · Full text
The progression of lung adenocarcinoma (LUAD) involves multiple molecular determinants, among which Oxysterol-binding protein-like 3 (OSBPL3) has been suggested to contribute to tumorigenesis, though its functional signi...
The progression of lung adenocarcinoma (LUAD) involves multiple molecular determinants, among which Oxysterol-binding protein-like 3 (OSBPL3) has been suggested to contribute to tumorigenesis, though its functional significance in LUAD remains poorly characterized. In this study, we elucidate the oncogenic functions and underlying mechanisms of OSBPL3 in LUAD pathogenesis. Analysis of clinical specimens revealed upregulated OSBPL3 expression in LUAD, which correlated with unfavorable patient outcomes. Genetic depletion of OSBPL3 in vitro impeded cellular proliferation, migratory capacity, and cell cycle progression, while inducing apoptotic cell death. Mechanistically, OSBPL3 was found to interact with the transcription factor NFE2L2, promoting its nuclear translocation and enhancing the transcriptional activation of PLAU, a downstream target gene. Upregulation of PLAU subsequently stimulated expression of key glycolytic enzymes through PI3K/AKT pathway activation, resulting in increased glucose consumption and lactate secretion. This metabolic reprogramming toward aerobic glycolysis facilitated malignant progression. Both genetic inhibition of PLAU and pharmacological blockade of AKT signaling abrogated the tumor-promoting phenotypes induced by OSBPL3. In vivo, OSBPL3 silencing significantly attenuated tumor growth and promoted apoptosis. Collectively, these findings identify an OSBPL3-NFE2L2-PLAU-AKT signaling axis that drives glycolytic metabolism and LUAD progression, showing its potential as a therapeutic target.
The novel tertiary amine LSD1 inhibitor 596 inhibits endometrial cancer through the mTOR signal transduction pathway.
Wang C, Shen D, Lin N … +7 more , Wang P, Bi Y, Hu H, Shang Y, Ren C, Yang L, Ma Q
Transl Oncol · 2026 Apr · PMID 41671780 · Full text
Lysine-specific demethylase 1 (LSD1) is a promising target in cancer therapy and plays an important role in the occurrence and development of tumors. However, research on LSD1 in endometrial cancer (EC) is indeed limited...
Lysine-specific demethylase 1 (LSD1) is a promising target in cancer therapy and plays an important role in the occurrence and development of tumors. However, research on LSD1 in endometrial cancer (EC) is indeed limited, and the related research on LSD1 inhibitors targeting EC is even rarer. In this study, our group developed a novel Tertiary Amine LSD1 inhibitor-596. 596 could specifically target LSD1 and inhibit the demethylation levels of H3K4me1/2 in a dose-dependent manner, thereby inhibited the proliferation of EC cells in vitro and in vivo. Moreover, in-depth studies have shown that 596 induces cell death in EC cells through the autophagy pathway, increasing the formation of autophagosomes and the expression of autophagy-related proteins. Transcriptomic sequencing revealed that 596-induced gene enrichment was related to the PI3K/AKT/mTOR pathway. The treatment group of 596 was able to attenuate the activation of the mTOR signaling cascade, and the combination treatment of 596 and the mTOR inhibitor rapamycin (RAPA) effectively reduced the survival rate, migration ability, and invasion ability of EC cells. Further studies in vitro and in vivo indicated that 596 could reduce the feedback activation of AKT mediated by the mTOR inhibitor rapamycin. In summary, our findings demonstrate that the LSD1 inhibitor 596 enhances the activity of the mTOR inhibitor by attenuating the feedback activation of AKT. LSD1 may be as a potential therapeutic target in EC, and LSD1 inhibitors represent an important therapeutic strategy in EC treatment.
Multi-omics analysis of NET+ TAN explains the immunosuppressive TME and prognosis value of malignant clinical characteristics in TNBC.
Zhu Q, Zheng X, Zhu X … +2 more , Yang P, Yang M
Transl Oncol · 2026 Apr · PMID 41671779 · Full text
Triple-negative breast cancer (TNBC) continues to exhibit a poor response to both immunotherapy and endocrine therapy, primarily due to its complex genetic heterogeneity and tumor immune microenvironment (TIME). Neutroph...
Triple-negative breast cancer (TNBC) continues to exhibit a poor response to both immunotherapy and endocrine therapy, primarily due to its complex genetic heterogeneity and tumor immune microenvironment (TIME). Neutrophil extracellular traps (NETs) are involved in neutrophil development and degranulation in treatment-resistant tumors, particularly TNBC and metastatic cases. Using a combination of single-cell RNA sequencing (scRNA-seq) datasets, bulk mRNA sequencing data from The Cancer Genome Atlas (TCGA) cohort, microarray data from the METABRIC and GEO databases, and epigenetic sequencing resources, we comprehensively investigated the functional characteristics and prognostic potential of NET-positive tumor-associated neutrophils (NET+ TAN) in TNBC. A six-gene panel derived from NET+ TAN has been identified as a reliable diagnostic biomarker for the survival of patients with TNBC and has been validated across several independent cohorts. Notably, our findings indicate that NET+ TAN facilitate T cell reprogramming in TNBC, thereby establishing a suppressive TIME and promoting tumor progression. This study provides a comprehensive perspective on the significance of NETs in patients with TNBC, with the aim of offering genetic and epigenetic insights into the mechanisms by which NETs may transition from cold to hot tumor phenotype, as well as valuable recommendations for therapeutic strategies.
SPP1⁺ macrophage-FADS1⁺ tumor cell crosstalk via the PDGFB-PDGFRB axis drives liver metastasis in colorectal cancer.
Zhao P, Pei F, Liu Y … +7 more , Jiang Y, Fang X, Shu L, Hu X, Chen F, Feng M, Li X
Transl Oncol · 2026 Apr · PMID 41655559 · Full text
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote this process remain...
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote this process remain poorly defined. Here, we developed an integrative multiomics framework to dissect the cellular and molecular determinants of colorectal cancer liver metastasis (CRLM). By analyzing 1,156 metastasis-associated genes, we identified three molecular subtypes with distinct prognostic and immunometabolic features: C1 with mixed phenotypes and favorable survival, C2 with metabolic activation and immune suppression, and C3 with immune activation and signaling dysregulation, which had the poorest outcomes. Mechanistically, we discovered that SPP1⁺ macrophages secrete PDGFB, which activates PDGFRB signaling in FADS1⁺ tumor cells to trigger epithelial-mesenchymal transition (EMT) and promote liver metastasis. This macrophage-tumor crosstalk was validated by single-cell transcriptomics, genetic perturbation, and coculture experiments. Collectively, our findings define a macrophage-derived PDGFB-PDGFRB axis that drives CRC liver metastasis and highlight a potential therapeutic target for overcoming metastatic progression and immune resistance.
Application of radiomics in head and neck squamous cell carcinoma.
Wu S, Wang Z, Zhang Y … +6 more , Chen Q, Liu H, Shen Y, Xiao J, Zhao L, Mao Y
Transl Oncol · 2026 Apr · PMID 41655558 · Full text
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent histopathological subtype of head and neck malignancies. Owing to the lack of early specific symptoms, the majority of patients are diagnosed at interme...
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent histopathological subtype of head and neck malignancies. Owing to the lack of early specific symptoms, the majority of patients are diagnosed at intermediate or advanced stages, which is associated with an unfavorable prognosis and a substantial decline in quality of life. Radiomics, which leverages large-scale medical imaging data, enables the extraction of high-dimensional quantitative features through advanced image analysis, thereby providing deeper insights into tumor biology. In this review, we summarize recent advances in radiomics for the diagnosis, prognostic prediction, and evaluation of treatment-related toxicity in HNSCC. Furthermore, we highlight emerging applications of radiomics in genomics and proteomics, illustrating the associations between tumor molecular phenotypes and imaging-derived features. Finally, we discuss the challenges related to feature standardization and reproducibility, and outline the key limitations of current radiomics studies.
Development and validation of prognostic nomograms based on peripheral blood T-cell counts and their dynamic changes for patients with nasopharyngeal carcinoma receiving radiotherapy.
Weng K, Lei Q, Hong Y … +4 more , Chen K, Sun Y, Wang Y, Zhu X
Transl Oncol · 2026 Apr · PMID 41655557 · Full text
AIM: To develop and validate prognostic nomograms incorporating peripheral blood lymphocyte counts and their dynamic changes in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. METHODS: In this retro...
AIM: To develop and validate prognostic nomograms incorporating peripheral blood lymphocyte counts and their dynamic changes in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. METHODS: In this retrospective cohort study, consecutive patients with NPC who received radiotherapy at Chongqing University Cancer Hospital were included as the internal cohort (randomly divided 70 %/30 % for training and validation), while patients treated at Guangxi Medical University Cancer Hospital served as the external validation cohort. Prognostic nomograms for progression-free survival (PFS) and overall survival (OS) were constructed using multivariable Cox regression analyses. RESULTS: The internal and external cohorts comprised 746 and 138 patients, respectively. Age, gross tumor volume dose, neoadjuvant chemotherapy, clinical stage, plasma EBV-DNA level, baseline total T-cell count, and its post-treatment change (ΔT cells) were identified as independent prognostic factors. The nomograms demonstrated strong predictive performance, with concordance indices of 0.701, 0.716, and 0.714 for PFS, and 0.759, 0.735, and 0.734 for OS in the training, internal validation, and external datasets, respectively. The areas under the receiver operating characteristic curves for 3-year and 5-year PFS and OS exceeded 0.7 across all cohorts. Calibration plots indicated good agreement between predicted and observed outcomes, and decision curve analysis confirmed greater net clinical benefit compared with TNM staging and EBV-DNA-based models. CONCLUSION: The proposed T-cell-based nomograms reliably predict PFS and OS in patients with NPC undergoing radiotherapy and were validated in an external cohort. These models provide improved prognostic discrimination beyond conventional staging systems and may assist in individualized risk stratification and management planning.
CMS subtypes correlate with complete response in trial of neoadjuvant Galunisertib plus chemoradiation in rectal cancer.
Rajamanickam V, Simons ND, Rosales W … +17 more , Kravchenko A, Yamazaki T, Bernard B, Piening B, Domingo E, Maughan T, Alvarez-Jimenez C, Desilvio T, Viswanath S, Whiteford M, Hayman A, O'Brien D, Kiely MX, Ahmad R, Gough MJ, Crittenden MR, Young KH
Transl Oncol · 2026 Apr · PMID 41653703 · Full text
Improving responses to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalatio...
Improving responses to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalation or de-escalation from standard-of-care treatment remains an area of investigation. We previously reported the primary and secondary endpoints of our single-arm study combining transforming growth factor beta receptor inhibitor, Galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Here we analyze RNA sequencing data obtained from tissue biopsies at baseline and after 2 weeks of galunisertib. Differences in expression of genes associated with MYC, inflammation, and epithelial-to-mesenchymal transition were observed between complete responders (CR) and <CR, with galunisertib upregulating MYC pathway expression in CR. Radiosensitivity and TGFβ response scores demonstrated limited ability to predict for response to galunisertib + chemoradiation. Typically treatment-resistant consensus molecular subtype 4 (CMS4), characterized by TGFβ expression, and metabolic subtype (CMS3) were associated with response to galunisertib + chemoradiation. Differences in correlations between RNA based measures of cell composition and immunohistologic quantification of infiltrates and extracted MRI parameters were observed for CIBERSORT, MCPcounter, and xCell methodologies. Based on these data, we hypothesize that the stromal radioresistant phenotype driven by TGFβ can be overcome by the addition of galunisertib to chemoradiation in rectal cancer.
Computed tomography- and magnetic resonance imaging-based multi-modality radiomics models for predicting survival in esophageal cancer patients.
Chu F, Li D, Wang Z … +6 more , Bai B, Zhao K, Wang S, Wang C, Yang G, Qu J
Transl Oncol · 2026 Mar · PMID 41650806 · Full text
OBJECTIVES: This study explores the integration of radiomics features from contrast-enhanced CT and MRI with clinical and radiological risk factors for optimal prognosis models of disease-free survival (DFS) and overall...
OBJECTIVES: This study explores the integration of radiomics features from contrast-enhanced CT and MRI with clinical and radiological risk factors for optimal prognosis models of disease-free survival (DFS) and overall survival (OS) in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A retrospective study is undertaken of 371 ESCC patients who underwent contrast-enhanced CT and MRI with StarVIBE sequence, from September 2014 to December 2019. Prognosis models for DFS and OS were developed using cross-validation and Elastic-Net-Cox regression. Patients were grouped by treatment type (surgery, chemoradiotherapy, neoadjuvant therapy) to create single-modality and multi-modality models (Model-S, Model-CRT, and Model-nT). Model performance was evaluated using nomograms, calibration curves, and decision curves. RESULTS: Twelve optimal prognosis models were identified. For DFS, MRI c-indices were 0.595, 0.608, and 0.721, while CT c-indices were 0.686, 0.616, and 0.667. For OS, MRI c-indices were 0.692, 0.597, and 0.650, and CT c-indices were 0.656, 0.623, and 0.695. Multi-modality models demonstrated c-indices of 0.750, 0.695, 0.839 for DFS and 0.898, 0.777, 0.819 for OS. CONCLUSION: Single-modality radiomics models exhibit limited predictive ability for DFS and OS in ESCC patients, whereas multi-modality radiomics models enhance predictive accuracy significantly.
Improving photodynamic therapy efficacy in bladder cancer using polymer micelle-encapsulated pheophorbide a.
Labroy M, Chabaud S, Durand M … +4 more , Fourquaux I, Bolduc S, Bordeleau F, Gibot L
Transl Oncol · 2026 Mar · PMID 41650805 · Full text
BACKGROUND: Photodynamic diagnosis (PDD) is widely used in bladder cancer management, enabling fluorescence-guided detection of lesions through intravesical administration of photosensitizers such as hexaminolevulinate (...
BACKGROUND: Photodynamic diagnosis (PDD) is widely used in bladder cancer management, enabling fluorescence-guided detection of lesions through intravesical administration of photosensitizers such as hexaminolevulinate (Cysview®/Hexvix®). Building on this clinical framework, we explored photodynamic therapy (PDT) using pheophorbide a (pheo), a chlorophyll-based photosensitizer, encapsulated in self-assembled poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) micelles. RESULTS: In vitro assays were performed on human bladder cancer cell lines, namely the grade 3 invasive T24 and the grade 1 SW780, in both 2D monolayers and 3D spheroid cultures. In 2D, encapsulated pheo showed higher phototoxicity (IC₅₀: 129 nM T24, 156 nM SW780), while free pheo exhibited negligible effects, preventing IC₅₀ determination. Two-photon microscopy confirmed that encapsulation markedly enhanced pheo penetration, especially in T24. SW780 spheroids exhibited tight epithelial features and low permeability, forming characteristic microbladder-like vesicles. PDT reduced viability in both T24 and SW780 3D models, with a significant advantage for encapsulated pheo at day 6 post-treatment in T24 spheroids. Preliminary exploration in human tissue-engineered bladder tumor substitutes demonstrated the feasibility for PDT assessment in complex 3D environments, warranting further study. CONCLUSIONS: These findings support polymer nanocarrier-mediated pheo delivery as a promising therapeutic approach and pave the way for integrated diagnostic-therapeutic strategies using existing intravesical platforms.
Oncogenic role of talin-1 in glioma: Association with poor prognosis and regulation of the TGF-beta signaling pathway.
Li J, Zhang D, Zhou H … +9 more , Hou L, Wang Y, Zhang Z, Wang Y, Li X, Yi L, Liu X, Wang Y, Xue X
Transl Oncol · 2026 Mar · PMID 41643630 · Full text
TLN1, a cytoskeletal protein associated with various tumors, remains inadequately studied in gliomas. In this study, we examined the functional role and mechanisms of TLN1 in glioma pathogenesis. Utilizing public databas...
TLN1, a cytoskeletal protein associated with various tumors, remains inadequately studied in gliomas. In this study, we examined the functional role and mechanisms of TLN1 in glioma pathogenesis. Utilizing public databases, we conducted differential expression, survival (Kaplan-Meier/ROC), and regression analyses, which were subsequently validated with institutional datasets and clinical tissues. In vitro experiments demonstrated that TLN1 knockdown in glioma cells resulted in reduced proliferation (CCK8/EDU), migration and invasion (wound healing/Transwell), and increased apoptosis (AO/EB/flow cytometry); these findings were corroborated by Western blot analyses. Gene Set Enrichment Analysis (GSEA) linked TLN1 to the TGF-beta signaling pathway, a connection further validated by Western blot and in vivo murine models. Both public and institutional data indicated that TLN1 was upregulated in gliomas, with elevated expression correlating with poor prognosis. Furthermore, TLN1 knockdown inhibited glioma growth and progression in vitro and in vivo, primarily through the TGF-beta signaling pathway. Our findings establish TLN1 as an oncogenic driver in gliomas and highlight its potential as a therapeutic target.
Ferroptosis induction enhances anti-PD-1 efficacy in NSCLC via HIF-1α/PD-L1 modulation.
Wang Z, Liu H, Liang J … +7 more , Zhang Y, Cho WC, Ye M, Ma D, Kong M, Zhu C, Shen J
Transl Oncol · 2026 Mar · PMID 41587523 · Full text
BACKGROUND: The monotherapeutic efficacy of immune checkpoint inhibitors (ICIs) remains unsatisfactory in patients suffering from non-small-cell lung cancer (NSCLC). Ferroptosis, an iron-dependent cell death process, has...
BACKGROUND: The monotherapeutic efficacy of immune checkpoint inhibitors (ICIs) remains unsatisfactory in patients suffering from non-small-cell lung cancer (NSCLC). Ferroptosis, an iron-dependent cell death process, has been identified as a promising immunotherapy adjuvant; however, ferroptosis inducers (such as erastin, RSL3) may paradoxically up-regulate hypoxia-inducible factor 1α (HIF-1α) and programmed death ligand 1 (PD-L1) to propel tumor immune evasion. It is critical to explore the molecular mechanism of ferroptosis in NSCLC immunotherapy and verify the efficacy of combined regimens for overcoming ICI limitations clinically. METHODS: This work analyzed 162 NSCLC patients receiving immunotherapy retrospectively to evaluate correlation between PD-L1 expression and progression-free survival (PFS). In vitro, CCK-8 assay, flow cytometry, qPCR, and Western blotting were utilized to measure impacts of ferroptosis inducers (Erastin, RSL3) upon cell viability, reactive oxygen species (ROS) levels, and PD-L1/HIF-1α expression in A549/H1299 NSCLC cells; ferroptosis-specific effects were validated by means of iron chelators (DFO, ferrostatin-1). In vivo, subcutaneous tumor models were built in C57BL/6 mice with LLC cells; therapeutic effects of ferroptosis inducer (IKE) alone or combined with anti-PD-1 antibody were evaluated through tumor weight measurement and immunohistochemistry (IHC). HIF-1α binding to PD-L1 promoter was confirmed via chromatin immunoprecipitation (ChIP); related signaling pathways were explored using transcriptome sequencing and KEGG enrichment analysis. RESULTS: For NSCLC patients who received immunotherapy, high PD-L1 expression correlated with longer PFS, and 4-HNE was associated positively with PD-L1 and CD8⁺T infiltration. In vitro, Erastin/RSL3 induced dose-dependent cell death, ROS accumulation, and PD-L1 up-regulation, reversed by iron chelators. In vivo, IKE+anti-PD-1 inhibited tumor growth significantly, whereas it increased CD8⁺T infiltration. Mechanistically, Erastin up-regulated HIF-1α via PI3K-AKT, which bound PD-L1 promoter (ChIP-verified), reversed by iron chelators. CONCLUSIONS: Ferroptosis inducers have dual effects in NSCLC, namely, promoting tumor cell death and triggering PD-L1-dependent immune evasion via the PI3K-AKT-HIF-1α pathway. However, combining ferroptosis inducers with anti-PD-1 antibodies retains the anti-tumor effect of ferroptosis and overcomes immune evasion by obstructing the PD-L1 pathway, offering a novel strategy for enhancing NSCLC immunotherapy efficacy.
Utilization of machine learning algorithms for the identification of the RLN associated prognostic model and feature biomarkers of RLN-related subtypes in breast cancer.
Du Y, Yuan Q, Yu H … +5 more , Ye R, Lin H, Yu G, Niu M, Qiu H
Transl Oncol · 2026 Mar · PMID 41581316 · Full text
BACKGROUND: Breast cancer (BC) is the most common malignancy afflicting women worldwide, yet the role of relaxin-related genes (RLN) in BC progression remains unclear. This study aims to elucidate the relationship betwee...
BACKGROUND: Breast cancer (BC) is the most common malignancy afflicting women worldwide, yet the role of relaxin-related genes (RLN) in BC progression remains unclear. This study aims to elucidate the relationship between RLN and BC outcomes through immune microenvironment and metabolic pathway analysis. METHODS: Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Relaxin-related genes were identified using KEGG and Genecard databases. A prognostic model, the RLN Associated Prognostic Model (TRAPM), was established using 101 combinations of 10 machine learning algorithms and validated at the single-cell level. Multi-omics analysis, including the IMvigor210 cohort, was performed to assess TRAPM's applicability in immunotherapy and drug selection. RESULTS: TRAPM, comprising nine prognostic genes (MMP1, RXFP1, PRKCZ, JUN, NFKBIA, GNAI2, NOS2, MMP9, and MMP13), showed significant associations with immune and metabolic profiles. Using TRAPM, a novel BC subtype RC3 and its key marker genes (MTHFD1L, CAVIN4, MMP1, ADGRG6, B3GNT5, SMYD2, and TFRC) were identified. Experimental validation through RT-qPCR and Western Blot confirmed the role of these markers in six BRCA cell lines. CONCLUSIONS: The identification of TRAPM and the RC3 subtype enhances our understanding of BC heterogeneity and highlights potential therapeutic targets. This study provides a foundation for personalized treatment strategies by clarifying the biological significance and clinical relevance of the RC3 subtype.
NPM1c⁺-driven lncRNA dysregulation in AML: Mechanisms, Controversies and translational roadblocks.
Zhang Q, Fu Y, Zhang J
Transl Oncol · 2026 Mar · PMID 41581315 · Full text
In the landscape of acute myeloid leukemia (AML) research, mutations in nucleophosmin 1 (NPM1) are the most prevalent genetic alterations. The leukemogenic mutant variant, NPM1c⁺, is associated with a distinct gene expre...
In the landscape of acute myeloid leukemia (AML) research, mutations in nucleophosmin 1 (NPM1) are the most prevalent genetic alterations. The leukemogenic mutant variant, NPM1c⁺, is associated with a distinct gene expression profile linked to leukemia, but the downstream oncogenic pathways remain only partially understood. Long non-coding RNAs (lncRNAs) are RNA molecules with known regulatory roles in human development and disease. Research implicates many lncRNAs in hematopoiesis and leukemogenesis, revealing correlations between their expression and clinical parameters in AML patients. While NPM1c⁺ AML exhibits a distinct lncRNA signature, it remains contentious whether these molecules are bona fide drivers or passenger events, and how their context-dependent functions can be therapeutically exploited. This review focuses on lncRNAs in NPM1c⁺ AML, highlighting their roles in pathogenesis, prognosis, and chemoresistance. By systematically elucidating the role of lncRNAs as pivotal factors in the diagnosis, treatment, and prognosis of NPM1c⁺ AML, this study addresses a gap in the existing literature. Our analysis of specific lncRNAs, such as HOTAIRM1, HOXB-AS3, CRNDE, HOXBLINC, LONA, IFEX9, XLOC_109948, and HOTTIP, enhances our understanding of the molecular mechanisms underlying AML in the context of NPM1c⁺. These findings lay the groundwork for developing targeted therapies and improved prognostic tools for NPM1c⁺AML.
An exploratory study on the relationship between renal cell carcinoma and CAFs infiltration by integrating Pathomics and collagen features.
Wang R, Jiang M, Li Z … +2 more , Zhao Z, Shen J
Transl Oncol · 2026 Mar · PMID 41579564 · Full text
OBJECTIVE: Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a significant role in renal cell carcinoma (RCC) progression and treatment response. However, current method...
OBJECTIVE: Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a significant role in renal cell carcinoma (RCC) progression and treatment response. However, current methods for evaluating CAFs infiltration in RCC are inadequate. This study aims to develop a non-invasive histopathological model based on H&E staining and collagen features to predict CAFs infiltration and investigate its prognostic value and biological relevance. METHODS: We conducted a retrospective analysis using H&E pathological images and clinical data from The Cancer Genome Atlas (TCGA) database. A Pathomics model integrating 465 histopathological features was constructed using machine learning algorithms (n = 354) to predict CAFs infiltration. A preliminary technical validation was performed using multiphoton microscopy-based collagen quantification (n = 25) to assess the correlation between the Pathomics Score and CAF-related fibrotic activity. Enrichment analysis, immune cell infiltration profiling, and mutation analysis were employed to explore the biological mechanisms underlying the model. RESULTS: The Pathomics model demonstrated high predictive accuracy (AUC=0.813) and correlated significantly with collagen deposition (r = 0.66, P < 0.001). High Pathomics scores were independently associated with poor survival (HR=1.80, P = 0.003) and linked to key biological processes, including YAP/TAZ activation, extracellular matrix (ECM) remodeling, immune suppression (e.g., CD276, IDO1), and frequent mutations in VHL and PBRM1 (>40%). CONCLUSION: This study establishes the first H&E-based Pathomics framework for quantifying CAFs infiltration in RCC, providing a cost-effective and non-invasive tool for preliminary risk stratification. The model's strong correlation with collagen features and its ability to reveal underlying molecular mechanisms highlight its potential for potential value in understanding the stromal microenvironment, though further external validation is required for clinical translation.
Five-year survival of patients with non-small cell lung cancer treated with alkalization therapy.
Kachi S, Suzuki K, Hamaguchi R … +3 more , Narui R, Morikawa H, Wada H
Transl Oncol · 2026 Mar · PMID 41570466 · Full text
Acidic tumor microenvironments promote malignant progression, immune evasion, and drug resistance. This single-center retrospective cohort study evaluated whether, among patients with stage IV non-small cell lung cancer...
Acidic tumor microenvironments promote malignant progression, immune evasion, and drug resistance. This single-center retrospective cohort study evaluated whether, among patients with stage IV non-small cell lung cancer (NSCLC) who participated in a pragmatic "alkalization therapy"-defined as a low potential renal acid load diet plus oral sodium bicarbonate and/or potassium/sodium citrate-urinary pH was associated with long-term survival, and whether these associations differed by EGFR/ALK mutation status. Urinary pH was used as a surrogate marker of systemic alkalization. All consecutive patients with stage IV NSCLC who first attended Karasuma Wada Clinic between January 2014, and December 2019 were included (n = 203; EGFR/ALK mutation-negative, n = 100; EGFR/ALK mutation-positive, n = 103). All outpatients received standardized instruction in alkalization therapy. For each patient, a mean urine pH value (excluding the first visit) was calculated. Survival was analyzed using Kaplan-Meier methods with log-rank and Gehan-Breslow-Wilcoxon tests, and Cox proportional hazards regression models incorporating recurrence status and urine pH. Overall, the 5-year survival rate was 49·0 % and was similar by mutation status (EGFR/ALK mutation-positive, 49·9 %; EGFR/ALK mutation-negative, 48·6 %). Among EGFR/ALK mutation-negative patients, postoperative recurrence was associated with a more favorable outcome than de novo stage IV disease at initial diagnosis (5-year survival 65·5 % vs 42·0 %; log-rank p = 0·02). In this subgroup, a mean urine pH ≥7·5 was associated with superior 5-year survival (70·0 % vs 39·3 %; log-rank p = 0·04). Given potential confounding, this shows association-not a causal benefit. Urinary pH may serve as a pragmatic marker of acid-base status, particularly in EGFR/ALK-mutation-negative disease.
Tumor-stroma contributes to immunotherapeutic resistance in non-small cell lung cancer via SEMA3C-mediated immunosuppressive tumor microenvironment.
Zhang H, Lin H, Wang J … +6 more , Wu D, Wang Q, Mei J, Li Q, Zhu Y, Cai Y
Transl Oncol · 2026 Mar · PMID 41558146 · Full text
BACKGROUND: The tumor-stroma proportion (TSP) was a critical factor influencing clinical outcomes in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms driving TSP-associated aggressiveness...
BACKGROUND: The tumor-stroma proportion (TSP) was a critical factor influencing clinical outcomes in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms driving TSP-associated aggressiveness and its contribution to immune checkpoint blockade (ICB) resistance remained poorly understood. METHODS: Using H&E staining data from the TCGA-NSCLC cohort, patients were stratified into TSP-high and low groups. Transcriptomic profiling and single-cell RNA sequencing (scRNA-seq) were employed to identify the TSP signatures. Functional validation was conducted to investigate the role of SEMA3C in cancer-associated fibroblasts (CAFs) and its influence to tumor cells and T cells. RESULTS: TSP-high status independently predicted worse overall survival (OS) and correlated with ICB resistance. Transcriptomic analysis identified seven TSP-related genes enriched in stromal fibroblasts. Among these signatures, SEMA3C emerged as the key TSP biomarker associated with an immunosuppressive tumor microenvironment (TME) and ICB resistance in NSCLC. Functionally, SEMA3C knockdown in CAFs suppressed their migratory capacity and collagen production. Co-culture experiments demonstrated that compared to SEMA3C-knockdown CAFs, control CAFs significantly enhanced tumor cell migration and invasion while suppressing the activation and proliferation of CD8⁺ T cells. Strikingly, in vivo targeting of SEMA3C inhibited tumor growth. CONCLUSION: TSP served as an independent prognostic biomarker and predictor of ICB resistance in NSCLC. SEMA3C was identified as a crucial mediator within this axis, promoting tumor malignancy and fostering an immunosuppressive TME characterized by stromal remodeling and excluded anti-tumor immunity. This study established TSP as a clinically relevant stratification tool and revealed stromal-immune crosstalk.
Integrated multi-omics analysis of prognostic model and immune microenvironment in intrahepatic cholangiocarcinoma.
Li X, Wang Y, Yin X … +4 more , Hu J, Lu H, Li D, Wu M
Transl Oncol · 2026 Mar · PMID 41558145 · Full text
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy originating from the epithelial lining of second-order bile ducts. Despite advances in immunotherapy, which underscore the pivotal roles of T...
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy originating from the epithelial lining of second-order bile ducts. Despite advances in immunotherapy, which underscore the pivotal roles of T-cell dynamics and tumor microenvironment (TME) remodeling in anti-tumor immunity, iCCA remains a clinical challenge due to its rapid progression. Consequently, there is a pressing need for integrated multi-omics approaches to elucidate the immune landscape of iCCA and guide effective precision immunotherapy. METHODS: To comprehensively characterize iCCA, we integrated single-cell RNA-seq data for microenvironment analysis and bulk RNA-seq cohorts for prognostic model construction using machine learning, followed by external validation and functional experimental verification of key genes. RESULTS: Integrated single-cell and spatial transcriptomic analysis of iCCA uncovered interacting epithelial-fibroblast subpopulations and guided the machine learning-based derivation of a five-gene prognostic signature. Furthermore, spatial transcriptomics confirmed the physical co-localization between SPP1+ Macrophage and NDRG1+ CAF. Finally, functional experiments established that MT1X, a gene highly expressed in iCCA, drives tumor proliferation, migration, and invasion. CONCLUSION: This study establishes a prognostic model based on five key genes and elucidates their role in the immunosuppressive TME. MT1X was validated as a pro-tumorigenic factor, highlighting its potential as a therapeutic target.
RHOJ-induced chemotherapy resistance through epithelial-mesenchymal transition in drug-tolerant persister cells of head and neck cancer.
Ling HH, Huang CM, Hsieh MS … +5 more , Yadav VK, Fong IH, Kuo KT, Yeh CT, Tsai JT
Transl Oncol · 2026 Mar · PMID 41548474 · Full text
BACKGROUND: Building on our previous identification of TXNRD1 and RHOJ as mediators of immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC), this study investigates the role of RHOJ in regulating end...
BACKGROUND: Building on our previous identification of TXNRD1 and RHOJ as mediators of immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC), this study investigates the role of RHOJ in regulating endothelial markers and signaling pathways in drug-tolerant persister (DTP) cells, as well as its contribution to immune suppression within the resistant tumor microenvironment. METHODS: We examined the role of RHOJ in regulating tumor-associated macrophage polarization and enhancing M1 antitumor activity and evaluated the therapeutic potential of targeting the RHOJ/Rho kinase axis in an HNSCC DTP mouse model. RESULTS: RHOJ expression was significantly upregulated in HNSCC DTP cells. RHOJ contributes to chemoresistance by increasing oxidative stress and initiating the DNA damage response. RNA sequencing revealed that the IPO9/EpCAM signaling pathway positively regulates RHOJ expression. Knockdown of RHOJ with shRNA suppressed HNSCC DTP cell migration and downregulated IPO9/EpCAM signaling. Gene enrichment analysis revealed high RHOJ expression in tumor-associated endothelial cells. Treatment with the RHOJ-dependent F-actin inhibitor Latrunculin B (HY-101,848) impaired actin polymerization and increased the chemosensitivity of HNSCC DTP cells. Silencing RHOJ inhibited M2 tumor-associated macrophage activation. RHOJ overexpression promoted M2 macrophage proliferation. CONCLUSION: RHOJ plays a critical role in modulating immunosuppressive signaling in both tumor and endothelial cells. RHOJ promotes the function of tumor-associated endothelial cells and drives EMT through its interaction with the IPO9/EpCAM signaling pathway, thereby increasing cell survival and drug resistance. Additionally, RHOJ may limit immune cell infiltration into the tumor core and promote immune evasion by contributing to vascular abnormalities and impaired barrier function.
Diagnostic efficacy of blood biomarkers for differentiating early-stage pancreatic cancer from chronic pancreatitis: A systematic review and network meta-analysis.
Wu D, Du ZK, Wang YC … +7 more , Zheng YZ, Qi HM, Zhu YR, Cao Y, Wang L, Zou WB, Liao Z
Transl Oncol · 2026 Mar · PMID 41547146 · Full text
BACKGROUND: Early diagnosis of pancreatic cancer (PC) remains challenging, particularly in patients with chronic pancreatitis (CP). Currently, imaging is often inaccurate and biopsy is inherently invasive. This is the fi...
BACKGROUND: Early diagnosis of pancreatic cancer (PC) remains challenging, particularly in patients with chronic pancreatitis (CP). Currently, imaging is often inaccurate and biopsy is inherently invasive. This is the first network meta-analysis (NMA) comparing blood-based biomarkers for differentiating PC from CP. METHODS: PubMed and EMBASE were searched for studies evaluating blood-based biomarkers for distinguishing PC from CP. Risk of bias was assessed with QUADAS-2. We conducted individual biomarker meta-analysis with generalized bivariate models. For the NMA, we applied a Bayesian inference approach via a Markov-chain Monte Carlo random effects model. The surface under the cumulative ranking curve was used to rank the diagnostic performance of the biomarkers. RESULTS: Across 139 enrolled studies, 49 biomarkers or panels were analyzed. For differentiating PC from CP, tumor polypeptide antigen (TPA) had the highest area under the summary receiver operating characteristic curve (AUSROC) (0.92). The NMA revealed that microRNA-196b (miR-196b) ranked highest in sensitivity (OR 3.74e+27), while the combination of carbohydrate antigen 19-9 (CA199) and a panel of eight extracellular vesicle long RNAs (exLRs) exhibited the highest specificity (OR 3.78). For early-stage (stage I and II) PC, the eight exLRs showed the highest relative sensitivity (OR 7.00), and carcinoembryonic antigen (CEA) demonstrated the highest specificity (OR 4.70). CONCLUSION: CA199 demonstrated only moderate diagnostic discrimination between PC and CP, with reduced efficacy in early-stage PC. Combining CA199 and eight exLRs exhibited promising differential diagnostic efficacy with both high sensitivity and specificity.
Advances in FLASH radiation therapy: A review on biological foundations and clinical prospects.
Di Y, Meng L, Wang Y … +1 more , Li J
Transl Oncol · 2026 Mar · PMID 41547145 · Full text
This paper provides a comprehensive review of the fundamental theories, clinical practices, technological advancements, current status, and future prospects of FLASH radiation therapy (FLASH-RT). As an emerging technique...
This paper provides a comprehensive review of the fundamental theories, clinical practices, technological advancements, current status, and future prospects of FLASH radiation therapy (FLASH-RT). As an emerging technique, FLASH-RT offers the potential to enhance therapeutic efficacy while minimizing damage to healthy tissues. We elaborate on the physical principles of the "FLASH effect" in radiation biology and its dose-distribution characteristics, describe clinical applications in tumor treatment, and evaluate protective effects on normal tissues. Furthermore, the review discusses technical advancements in equipment, dosimetry, and imaging, while analyzing current research hotspots and technical bottlenecks. We also examine pathological mechanisms, future applications, and prevailing controversies regarding safety, efficacy uncertainty, and ethics. This comprehensive discussion provides a valuable reference for deepening the understanding of FLASH-RT's translational journey.
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