Pub Date : 2026-02-07DOI: 10.1016/j.tranon.2026.102696
Pingfan Zhao , Fuyong Pei , Yanmin Liu , Yinan Jiang , Xiaochang Fang , Lin Shu , Xin Hu , Feiyang Chen , Maohui Feng , Xuanfei Li
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.
{"title":"SPP1⁺ macrophage-FADS1⁺ tumor cell crosstalk via the PDGFB-PDGFRB axis drives liver metastasis in colorectal cancer","authors":"Pingfan Zhao , Fuyong Pei , Yanmin Liu , Yinan Jiang , Xiaochang Fang , Lin Shu , Xin Hu , Feiyang Chen , Maohui Feng , Xuanfei Li","doi":"10.1016/j.tranon.2026.102696","DOIUrl":"10.1016/j.tranon.2026.102696","url":null,"abstract":"<div><div>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.</div><div>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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"66 ","pages":"Article 102696"},"PeriodicalIF":5.0,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.tranon.2025.102661
Kegui Weng , Qianqian Lei , Ye Hong , Kaihua Chen , Yongchu Sun , Ying Wang , Xiaodong Zhu
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.
{"title":"Development and validation of prognostic nomograms based on peripheral blood T-cell counts and their dynamic changes for patients with nasopharyngeal carcinoma receiving radiotherapy","authors":"Kegui Weng , Qianqian Lei , Ye Hong , Kaihua Chen , Yongchu Sun , Ying Wang , Xiaodong Zhu","doi":"10.1016/j.tranon.2025.102661","DOIUrl":"10.1016/j.tranon.2025.102661","url":null,"abstract":"<div><h3>Aim</h3><div>To develop and validate prognostic nomograms incorporating peripheral blood lymphocyte counts and their dynamic changes in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"66 ","pages":"Article 102661"},"PeriodicalIF":5.0,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.tranon.2026.102689
Siyi Wu , Zaiyu Wang , Yu Zhang , Qi Chen , Honghao Liu , Yedong Shen , Juxiong Xiao , Luqing Zhao , Yitao Mao
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.
{"title":"Application of radiomics in head and neck squamous cell carcinoma","authors":"Siyi Wu , Zaiyu Wang , Yu Zhang , Qi Chen , Honghao Liu , Yedong Shen , Juxiong Xiao , Luqing Zhao , Yitao Mao","doi":"10.1016/j.tranon.2026.102689","DOIUrl":"10.1016/j.tranon.2026.102689","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"66 ","pages":"Article 102689"},"PeriodicalIF":5.0,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.tranon.2026.102690
Venkatesh Rajamanickam , Noah D. Simons , Wesley Rosales , Anton Kravchenko , Tomoko Yamazaki , Brady Bernard , Brian Piening , Enric Domingo , Timothy Maughan , Charlems Alvarez-Jimenez , Thomas Desilvio , Satish Viswanath , Mark Whiteford , Amanda Hayman , David O’Brien , Maria X. Kiely , Rehan Ahmad , Michael J. Gough , Marka R. Crittenden , Kristina H. Young
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.
{"title":"CMS subtypes correlate with complete response in trial of neoadjuvant Galunisertib plus chemoradiation in rectal cancer","authors":"Venkatesh Rajamanickam , Noah D. Simons , Wesley Rosales , Anton Kravchenko , Tomoko Yamazaki , Brady Bernard , Brian Piening , Enric Domingo , Timothy Maughan , Charlems Alvarez-Jimenez , Thomas Desilvio , Satish Viswanath , Mark Whiteford , Amanda Hayman , David O’Brien , Maria X. Kiely , Rehan Ahmad , Michael J. Gough , Marka R. Crittenden , Kristina H. Young","doi":"10.1016/j.tranon.2026.102690","DOIUrl":"10.1016/j.tranon.2026.102690","url":null,"abstract":"<div><div>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 <em>MYC</em> 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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"66 ","pages":"Article 102690"},"PeriodicalIF":5.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.tranon.2026.102687
Maxime Labroy , Stéphane Chabaud , Maud Durand , Isabelle Fourquaux , Stéphane Bolduc , François Bordeleau , Laure Gibot
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) (PEO5000-PCL4000) 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.
{"title":"Improving photodynamic therapy efficacy in bladder cancer using polymer micelle-encapsulated pheophorbide a","authors":"Maxime Labroy , Stéphane Chabaud , Maud Durand , Isabelle Fourquaux , Stéphane Bolduc , François Bordeleau , Laure Gibot","doi":"10.1016/j.tranon.2026.102687","DOIUrl":"10.1016/j.tranon.2026.102687","url":null,"abstract":"<div><h3>Background</h3><div>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 <em>a</em> (pheo), a chlorophyll-based photosensitizer, encapsulated in self-assembled poly(ethylene oxide)-block-poly(<em>ε</em>-caprolactone) (PEO<sub>5000</sub>-PCL<sub>4000</sub>) micelles.</div></div><div><h3>Results</h3><div><em>In vitro</em> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102687"},"PeriodicalIF":5.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1016/j.tranon.2026.102686
Funing Chu , Dexuan Li , Zhaoqi Wang , Bingmei Bai , Keke Zhao , Shuting Wang , Chenglong Wang , Guang Yang , Jinrong Qu
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.
{"title":"Computed tomography- and magnetic resonance imaging-based multi-modality radiomics models for predicting survival in esophageal cancer patients","authors":"Funing Chu , Dexuan Li , Zhaoqi Wang , Bingmei Bai , Keke Zhao , Shuting Wang , Chenglong Wang , Guang Yang , Jinrong Qu","doi":"10.1016/j.tranon.2026.102686","DOIUrl":"10.1016/j.tranon.2026.102686","url":null,"abstract":"<div><h3>Objectives</h3><div>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).</div></div><div><h3>Materials and Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Single-modality radiomics models exhibit limited predictive ability for DFS and OS in ESCC patients, whereas multi-modality radiomics models enhance predictive accuracy significantly.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102686"},"PeriodicalIF":5.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1016/j.tranon.2026.102691
Jiayuan Li , Dongdong Zhang , Huandi Zhou , Liubing Hou , Yu Wang , Zizhou Zhang , Yanqiang Wang , Xiuwu Li , Le Yi , Xiaomin Liu , Yongzhi Wang , Xiaoying Xue
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.
{"title":"Oncogenic role of talin-1 in glioma: Association with poor prognosis and regulation of the TGF-beta signaling pathway","authors":"Jiayuan Li , Dongdong Zhang , Huandi Zhou , Liubing Hou , Yu Wang , Zizhou Zhang , Yanqiang Wang , Xiuwu Li , Le Yi , Xiaomin Liu , Yongzhi Wang , Xiaoying Xue","doi":"10.1016/j.tranon.2026.102691","DOIUrl":"10.1016/j.tranon.2026.102691","url":null,"abstract":"<div><div><em>TLN1</em>, a cytoskeletal protein associated with various tumors, remains inadequately studied in gliomas. In this study, we examined the functional role and mechanisms of <em>TLN1</em> 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 <em>TLN1</em> 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 <em>TLN1</em> 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 <em>TLN1</em> was upregulated in gliomas, with elevated expression correlating with poor prognosis. Furthermore, <em>TLN1</em> knockdown inhibited glioma growth and progression in vitro and in vivo, primarily through the TGF-beta signaling pathway. Our findings establish <em>TLN1</em> as an oncogenic driver in gliomas and highlight its potential as a therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102691"},"PeriodicalIF":5.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.tranon.2026.102697
David Adeleke , Adewale Oluwaseun Fadaka , Nicole Remaliah Samantha Sibuyi , Ashwil Klein , Mervin Meyer , Gomes Rahul , Rick Jansen
Tumor Mutational Burden (TMB) is a widely used biomarker for selecting cancer patients for immune checkpoint inhibitor (ICI) therapy. However, TMB alone has limited predictive power, as it fails to account for the functional impact of mutations. We introduce AlphaTMB, a composite biomarker that integrates the quantity of mutations (TMB) with the qualitative assessment of their pathogenicity using AlphaMissense, a deep learning model that predicts the deleteriousness of missense variants. Using a pan-cancer cohort of 1,662 patients from the MSK-IMPACT study who received ICI therapy, we computed three scores per patient: TMB, Alpha (sum of AlphaMissense scores), and AlphaTMB (product of TMB and Alpha). Patients were stratified using both cancer-specific and pan-cancer quantiles. Survival outcomes were evaluated using Kaplan-Meier and multivariate Cox proportional hazards models, controlling for cancer type, age, and ICI regimen. AlphaTMB showed strong correlation with TMB (Spearman ρ = 0.866, p < 0.001), but offered improved prognostic accuracy. Patients in the bottom 80% AlphaTMB group had significantly poorer survival than those in the top 10% (HR < 2.51, p < 0.001), outperforming TMB and Alpha alone. AlphaTMB reclassified borderline cases, identifying subsets with low TMB but high deleterious mutation load, and vice versa. Gene mutation heatmaps and co-occurrence analysis confirmed that to 10% AlphaTMB-high tumors were enriched in mismatch repair and POLE mutations, reflecting a neoantigen-rich, immunotherapy-responsive phenotype. AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.
肿瘤突变负荷（Tumor Mutational Burden， TMB）是一种广泛使用的生物标志物，用于选择接受免疫检查点抑制剂（ICI）治疗的癌症患者。然而，TMB本身的预测能力有限，因为它无法解释突变对功能的影响。我们介绍了一种复合生物标志物alphaatmb，它将突变数量（TMB）与使用AlphaMissense（一种预测错义变异危害性的深度学习模型）对其致病性进行定性评估相结合。使用来自MSK-IMPACT研究的1,662例接受ICI治疗的泛癌症队列，我们计算了每位患者的三个评分：TMB， Alpha （AlphaMissense评分之和）和alphaatmb （TMB和Alpha的乘积）。采用癌症特异性分位数和泛癌症分位数对患者进行分层。使用Kaplan-Meier和多变量Cox比例风险模型评估生存结果，控制癌症类型、年龄和ICI方案。alphaatmb与TMB有很强的相关性（Spearman ρ = 0.866, p < 0.001），但可提高预后准确性。后80%的AlphaTMB组患者的生存率明显低于前10%的患者（HR < 2.51, p < 0.001），优于TMB和Alpha单独治疗。alphaatmb重新分类了临界病例，确定了低TMB但高有害突变负荷的亚群，反之亦然。基因突变热图和共现分析证实，高达10%的高alphatmb肿瘤富含错配修复和POLE突变，反映了一种富含新抗原、免疫治疗应答的表型。与单独的TMB相比，alphaatmb提高了生存预测，更好地捕获免疫原性肿瘤特征，并反映更准确的患者分层。这种人工智能衍生的体细胞突变致病性评分代表了个性化免疫肿瘤学的一步，值得在前瞻性研究中进一步验证。
{"title":"AlphaMissense pathogenicity scores predict response to immunotherapy and enhances the predictive capability of tumor mutation burden","authors":"David Adeleke , Adewale Oluwaseun Fadaka , Nicole Remaliah Samantha Sibuyi , Ashwil Klein , Mervin Meyer , Gomes Rahul , Rick Jansen","doi":"10.1016/j.tranon.2026.102697","DOIUrl":"10.1016/j.tranon.2026.102697","url":null,"abstract":"<div><div>Tumor Mutational Burden (TMB) is a widely used biomarker for selecting cancer patients for immune checkpoint inhibitor (ICI) therapy. However, TMB alone has limited predictive power, as it fails to account for the functional impact of mutations. We introduce AlphaTMB, a composite biomarker that integrates the quantity of mutations (TMB) with the qualitative assessment of their pathogenicity using AlphaMissense, a deep learning model that predicts the deleteriousness of missense variants. Using a pan-cancer cohort of 1,662 patients from the MSK-IMPACT study who received ICI therapy, we computed three scores per patient: TMB, Alpha (sum of AlphaMissense scores), and AlphaTMB (product of TMB and Alpha). Patients were stratified using both cancer-specific and pan-cancer quantiles. Survival outcomes were evaluated using Kaplan-Meier and multivariate Cox proportional hazards models, controlling for cancer type, age, and ICI regimen. AlphaTMB showed strong correlation with TMB (Spearman ρ = 0.866, <em>p</em> < 0.001), but offered improved prognostic accuracy. Patients in the bottom 80% AlphaTMB group had significantly poorer survival than those in the top 10% (HR < 2.51, <em>p</em> < 0.001), outperforming TMB and Alpha alone. AlphaTMB reclassified borderline cases, identifying subsets with low TMB but high deleterious mutation load, and vice versa. Gene mutation heatmaps and co-occurrence analysis confirmed that to 10% AlphaTMB-high tumors were enriched in mismatch repair and POLE mutations, reflecting a neoantigen-rich, immunotherapy-responsive phenotype. AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102697"},"PeriodicalIF":5.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, including Taiwan. It exhibits higher morbidity as well as mortality in males than in females. However, the role of the androgen receptor (AR) in NPC remains unclear. In this study, AR expression was detected in most NPC cell lines and patient-derived xenografts. Treatment with enzalutamide, an antiandrogen, substantially inhibited patient-derived xenografts growth and demonstrated additive antitumor effects when combined with chemotherapy in AR-positive models. Additionally, transcriptome analysis following enzalutamide treatment revealed activation of hypoxia-inducible factor-1, steroid hormone, and AR pathways, alongside suppression of interferon and tumor necrosis factor pathways. Protein analysis further supported these transcriptomic changes. In AR-overexpressing NPC-B13 cells, AR appeared to regulate thyroid transcription factor-1 (TTF-1, encoded by NKX2–1 gene) and its downstream target epidermal growth factor receptor (EGFR), thereby promoting cancer cell proliferation. Furthermore, chromatin immunoprecipitation suggested that AR may directly bind to the NKX2–1 promoter to upregulate its mRNA expression. Under AR overexpression, Epstein-Barr virus (EBV) remained in a latent state, accompanied by suppression of lytic gene expression. Additionally, Epstein–Barr nuclear antigen-1 enhanced AR transactivation in a dose-dependent manner in NPC cell line reporter assays. Among 96 metastatic NPC tumor samples, AR expression was observed in 35 cases (36.5%), predominantly in males (33/83, 39.8%). AR expression correlated with poorer overall survival, with statistical significance noted in the full cohort and particularly in male patients. This study suggests that AR may promote metastatic NPC progression via the TTF-1/EGFR signaling pathway and interact with EBV to influence disease behavior, especially in males.
{"title":"Androgen receptor may promote tumor progression via TTF-1/EGFR pathway in metastatic nasopharyngeal carcinoma","authors":"Chiao-Yun Lin , Chen-Yang Huang , Kar-Wai Lui, Yin-Kai Chao, Chun-Nan Yeh, Li-Yu Lee, Yenlin Huang, Zhangung Yang, Chia-Hsun Hsieh, Hsien-Chi Fan, An-Chi Lin, Kai-Ping Chang, Chien-Yu Lin, Hung-Ming Wang, Mei Chao, Yu-Sun Chang, Hsin-Pai Li, Cheng-Lung Hsu","doi":"10.1016/j.tranon.2026.102670","DOIUrl":"10.1016/j.tranon.2026.102670","url":null,"abstract":"<div><div>Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, including Taiwan. It exhibits higher morbidity as well as mortality in males than in females. However, the role of the androgen receptor (AR) in NPC remains unclear. In this study, AR expression was detected in most NPC cell lines and patient-derived xenografts. Treatment with enzalutamide, an antiandrogen, substantially inhibited patient-derived xenografts growth and demonstrated additive antitumor effects when combined with chemotherapy in AR-positive models. Additionally, transcriptome analysis following enzalutamide treatment revealed activation of hypoxia-inducible factor-1, steroid hormone, and AR pathways, alongside suppression of interferon and tumor necrosis factor pathways. Protein analysis further supported these transcriptomic changes. In AR-overexpressing NPC-B13 cells, AR appeared to regulate thyroid transcription factor-1 (TTF-1, encoded by <em>NKX2–1</em> gene) and its downstream target epidermal growth factor receptor (EGFR), thereby promoting cancer cell proliferation. Furthermore, chromatin immunoprecipitation suggested that AR may directly bind to the <em>NKX2–1</em> promoter to upregulate its mRNA expression. Under AR overexpression, Epstein-Barr virus (EBV) remained in a latent state, accompanied by suppression of lytic gene expression. Additionally, Epstein–Barr nuclear antigen-1 enhanced AR transactivation in a dose-dependent manner in NPC cell line reporter assays. Among 96 metastatic NPC tumor samples, AR expression was observed in 35 cases (36.5%), predominantly in males (33/83, 39.8%). AR expression correlated with poorer overall survival, with statistical significance noted in the full cohort and particularly in male patients. This study suggests that AR may promote metastatic NPC progression via the TTF-1/EGFR signaling pathway and interact with EBV to influence disease behavior, especially in males.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102670"},"PeriodicalIF":5.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
WNT1 inducible signaling pathway protein 1 (WISP1) is a connective tissue growth factor that regulates various cellular functions in different tissues but has yet to be examined in the human bladder. Two isoforms of WISP1 (WISP1v1 and WISP1v2) expressed only in bladder fibroblast (HBdSF) and smooth muscle (HBdSMC) cells but not in bladder cancer cells in vitro. TNF-α treatment-induced IL-6, CXCL5, and SDF-1 expressions in bladder stroma cells. TNF-α-induced IL-6 depends on the WISP1, and the TNF-α-activation was suppressed under CAPE treatment. WISP1-knockdown inhibited the proliferation and contraction of HBdSMC and HBdSF cells, while the conditioned media from either ectopic WISP1v1- or WISP1v2-overexpressed 293T cells stimulated both the proliferation of HBdSF and HBdSMC cells. The supernatant of WISP1-knockdown in HBdSMC cells reduced the migration of bladder carcinoma T24 cells. WISP1v1, but not WISP1v2, enhanced cell growth, migration, and invasion in bladder cancer cells via downregulating NDRG1, KAI1, and Maspin expressions. Silico's analysis confirmed that WISP1 is a potential oncogene in human bladder cancer. Results suggest that WISP1, a stroma-specific secreted protein, modulates the behavior of bladder stroma cells via autocrine signaling. WISP1 induces tumor growth of bladder carcinoma cells in an isoform-dependent manner via paracrine signaling, indicating that WISP1 may behave as a mediator linking diseases of the human bladder.
{"title":"WISP1 is the stromal-secreting oncoprotein via paracrine downregulation of NDRG1, KAI1, and Maspin in human bladder cancer cells","authors":"Syue-Ting Chen , Kang-Shuo Chang , Chen-Pang Hou , Wei-Yin Lin , Shu-Yuan Hsu , Hsin-Ching Sung , Tsui-Hsia Feng , Yu-Hsiang Lin , Horng-Heng Juang","doi":"10.1016/j.tranon.2026.102680","DOIUrl":"10.1016/j.tranon.2026.102680","url":null,"abstract":"<div><div>WNT1 inducible signaling pathway protein 1 (WISP1) is a connective tissue growth factor that regulates various cellular functions in different tissues but has yet to be examined in the human bladder. Two isoforms of WISP1 (WISP1v1 and WISP1v2) expressed only in bladder fibroblast (HBdSF) and smooth muscle (HBdSMC) cells but not in bladder cancer cells <em>in vitro</em>. TNF-α treatment-induced IL-6, CXCL5, and SDF-1 expressions in bladder stroma cells. TNF-α-induced IL-6 depends on the WISP1, and the TNF-α-activation was suppressed under CAPE treatment. WISP1-knockdown inhibited the proliferation and contraction of HBdSMC and HBdSF cells, while the conditioned media from either ectopic WISP1v1- or WISP1v2-overexpressed 293T cells stimulated both the proliferation of HBdSF and HBdSMC cells. The supernatant of WISP1-knockdown in HBdSMC cells reduced the migration of bladder carcinoma T24 cells. WISP1v1, but not WISP1v2, enhanced cell growth, migration, and invasion in bladder cancer cells via downregulating NDRG1, KAI1, and Maspin expressions. Silico's analysis confirmed that WISP1 is a potential oncogene in human bladder cancer. Results suggest that WISP1, a stroma-specific secreted protein, modulates the behavior of bladder stroma cells via autocrine signaling. WISP1 induces tumor growth of bladder carcinoma cells in an isoform-dependent manner via paracrine signaling, indicating that WISP1 may behave as a mediator linking diseases of the human bladder.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102680"},"PeriodicalIF":5.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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