Pub Date : 2026-02-01Epub Date: 2025-12-13DOI: 10.1016/j.tranon.2025.102645
Caitland A Love , John W Figg , Mia Engelbart , Illeana West , Catherine Flores
Glioblastoma (GBM) remains one of the most lethal brain malignancies, with an abysmal five-year survival rate near 6 %. Despite advances in tumor biology, clinical outcomes have not improved, partially due to glioma stem cells (GSCs) that drive treatment resistance. Radial glial cells (RGCs), recognized as key progenitors in neurodevelopment, have recently gained attention in GBM research due to RGC-like populations being identified in GBM. RGCs have striking similarities with GSCs, including their mechanisms of self-renewal, pluripotency, and migration. This review highlights those parallels between as well as recent studies on their critical intersections to expand our comprehension of neurodevelopmental paradigms in GBM. Understanding these parallels may uncover developmental pathways that can be exploited to improve therapeutic strategies for GBM.
{"title":"Radial glial cells and glioblastoma: how developmental neurobiology can inform our understanding of brain cancer initiation, treatment resistance, and resilience","authors":"Caitland A Love , John W Figg , Mia Engelbart , Illeana West , Catherine Flores","doi":"10.1016/j.tranon.2025.102645","DOIUrl":"10.1016/j.tranon.2025.102645","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most lethal brain malignancies, with an abysmal five-year survival rate near 6 %. Despite advances in tumor biology, clinical outcomes have not improved, partially due to glioma stem cells (GSCs) that drive treatment resistance. Radial glial cells (RGCs), recognized as key progenitors in neurodevelopment, have recently gained attention in GBM research due to RGC-like populations being identified in GBM. RGCs have striking similarities with GSCs, including their mechanisms of self-renewal, pluripotency, and migration. This review highlights those parallels between as well as recent studies on their critical intersections to expand our comprehension of neurodevelopmental paradigms in GBM. Understanding these parallels may uncover developmental pathways that can be exploited to improve therapeutic strategies for GBM.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102645"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757446","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 : 2026-02-01Epub Date: 2025-12-17DOI: 10.1016/j.tranon.2025.102639
Jiacheng Yin , Xing Jin , Zhengyang Hu , Huiqiang Yang , Shuhua Huo , Fenghao Sun , Wei Jiang , Qun Wang , Qihai Sui , Yu Shi , Zhencong Chen
Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers expression defines the CSC compartment, it provides little information on molecular mechanisms underlying the biological behaviors of CSCs. The CSC-driving tumor evolution path is also largely unknown due to technical difficulties. This study aimed to comprehensively depict the landscape of LUAD CSCs at the single-cell and molecular levels.
Through flow cytometry and lineage tracing, we reconstructed LUAD CSCs trajectories with patient-derived samples and identified a persistent stem-like population with distinct molecular signatures through all tumor stages. CSC-related pathways, transcription factors (TFs) and metabolic characteristics were differentially expressed along LUAD progression, which revealed that developmental trajectory and tumor heterogeneity were driven by multistep transcriptional reprogramming of CSCs. Moreover, CSCs might promote LUAD progression through the S100A9-pNF-κB axis. We discovered a specific stemness signature with genetic profiles along the tumor progression and significantly correlated with clinical outcomes. Notably, by integrating bulk tumor data from TCGA, molecular clustering based on the CSC stemness signature well-distinguished clinical features and genomic or immune alterations, with the high stemness index group exhibiting reduced immune activity and a tendency towards cold tumors.
Overall, our results provided unique perspectives into previously unappreciated molecular dynamics of CSC subpopulations driving LUAD evolution. The stemness signature tailored personalized risk assessment and immunotherapy strategies for individual LUAD patients.
{"title":"The stem cell atlas of lung adenocarcinoma: A stemness blueprint for prognosis and immunotherapy success","authors":"Jiacheng Yin , Xing Jin , Zhengyang Hu , Huiqiang Yang , Shuhua Huo , Fenghao Sun , Wei Jiang , Qun Wang , Qihai Sui , Yu Shi , Zhencong Chen","doi":"10.1016/j.tranon.2025.102639","DOIUrl":"10.1016/j.tranon.2025.102639","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers expression defines the CSC compartment, it provides little information on molecular mechanisms underlying the biological behaviors of CSCs. The CSC-driving tumor evolution path is also largely unknown due to technical difficulties. This study aimed to comprehensively depict the landscape of LUAD CSCs at the single-cell and molecular levels.</div><div>Through flow cytometry and lineage tracing, we reconstructed LUAD CSCs trajectories with patient-derived samples and identified a persistent stem-like population with distinct molecular signatures through all tumor stages. CSC-related pathways, transcription factors (TFs) and metabolic characteristics were differentially expressed along LUAD progression, which revealed that developmental trajectory and tumor heterogeneity were driven by multistep transcriptional reprogramming of CSCs. Moreover, CSCs might promote LUAD progression through the S100A9-pNF-κB axis. We discovered a specific stemness signature with genetic profiles along the tumor progression and significantly correlated with clinical outcomes. Notably, by integrating bulk tumor data from TCGA, molecular clustering based on the CSC stemness signature well-distinguished clinical features and genomic or immune alterations, with the high stemness index group exhibiting reduced immune activity and a tendency towards cold tumors.</div><div>Overall, our results provided unique perspectives into previously unappreciated molecular dynamics of CSC subpopulations driving LUAD evolution. The stemness signature tailored personalized risk assessment and immunotherapy strategies for individual LUAD patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102639"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782998","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 : 2026-02-01Epub Date: 2025-12-18DOI: 10.1016/j.tranon.2025.102648
Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng
Objective
: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).
Methods
: The anti-cancer effects of PG were systematically evaluated in vitro using PTC cell lines and in vivo via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.
Results
: In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both in vitro and in vivo, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity in vivo.
Conclusion
: PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.
{"title":"Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models","authors":"Meiyu Liu , Junwei Huang , Mengqiao Dai , Xiaoni Gao , Zihang Ai , Wei Hu , Zanbing Li , feijie wang , Junjie Yang , Haidong Liao , Yang Xie , Yong Ying , Xiangtai Zeng","doi":"10.1016/j.tranon.2025.102648","DOIUrl":"10.1016/j.tranon.2025.102648","url":null,"abstract":"<div><h3>Objective</h3><div><strong>:</strong> To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC).</div></div><div><h3>Methods</h3><div><strong>:</strong> The anti-cancer effects of PG were systematically evaluated <em>in vitro</em> using PTC cell lines and <em>in vivo</em> via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry.</div></div><div><h3>Results</h3><div><strong>:</strong> In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both <em>in vitro</em> and <em>in vivo</em>, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div><strong>:</strong> PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102648"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795007","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 : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.tranon.2025.102643
Diana Lourenço , Raquel Lopes , Joana Caetano , Filipa Barahona , Jessica Rodrigues , Ana C. Queirós , Emilie Arnault Carneiro , Cristina João
Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation.
We developed BioMarrow, a 3D ex vivo BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays.
The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity.
BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for ex vivo therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.
{"title":"BioMarrow: An accessible and reproducible 3D patient-derived bone marrow model for advancing research and clinical applications","authors":"Diana Lourenço , Raquel Lopes , Joana Caetano , Filipa Barahona , Jessica Rodrigues , Ana C. Queirós , Emilie Arnault Carneiro , Cristina João","doi":"10.1016/j.tranon.2025.102643","DOIUrl":"10.1016/j.tranon.2025.102643","url":null,"abstract":"<div><div>Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation.</div><div>We developed BioMarrow, a 3D <em>ex vivo</em> BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays.</div><div>The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity.</div><div>BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for <em>ex vivo</em> therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102643"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798221","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 : 2026-02-01Epub Date: 2026-01-06DOI: 10.1016/j.tranon.2025.102660
Li-Jin Xie , Li-Li Fu , Shu-Cen Liu , Chang-Sen Bai , Bai-Cheng Xu , Xiong-Wen He , Hai-Feng Lin , Yue-Can Zeng , Wen-Jun Tang
Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the “Four-Dimensional TNMB Staging System,” which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification.
Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of “monitoring-intervention-remonitoring,” establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.
{"title":"Adaptive therapy for perioperative non–small cell lung cancer: strategies guided by dynamic minimal residual disease adjustment","authors":"Li-Jin Xie , Li-Li Fu , Shu-Cen Liu , Chang-Sen Bai , Bai-Cheng Xu , Xiong-Wen He , Hai-Feng Lin , Yue-Can Zeng , Wen-Jun Tang","doi":"10.1016/j.tranon.2025.102660","DOIUrl":"10.1016/j.tranon.2025.102660","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the “Four-Dimensional TNMB Staging System,” which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification.</div><div>Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of “monitoring-intervention-remonitoring,” establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102660"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913223","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 : 2026-02-01Epub Date: 2025-12-17DOI: 10.1016/j.tranon.2025.102652
Qiao Peng , Mengmei Zhang , Shuyu Zhao , Yadong Guo , Minjue Shan , Baimei Su , Shiyu Mao , Donghui Shi , Ziyou Lin
Introduction
Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear.
Methods
We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan–Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.
Results
AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.
Conclusions
Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.
{"title":"Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer","authors":"Qiao Peng , Mengmei Zhang , Shuyu Zhao , Yadong Guo , Minjue Shan , Baimei Su , Shiyu Mao , Donghui Shi , Ziyou Lin","doi":"10.1016/j.tranon.2025.102652","DOIUrl":"10.1016/j.tranon.2025.102652","url":null,"abstract":"<div><h3>Introduction</h3><div>Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear.</div></div><div><h3>Methods</h3><div>We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan–Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.</div></div><div><h3>Results</h3><div>AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.</div></div><div><h3>Conclusions</h3><div>Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102652"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782969","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 : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.tranon.2025.102641
Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin
Background
Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.
Methods
Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).
Results
EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, P < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, P < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, P < 0.001), with 78.6 % sensitivity and 97.5 % specificity.
Conclusions
Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.
鼻咽癌（NPC）是头颈癌的一个亚型。本研究旨在探讨EphB2在鼻咽癌中的诊断及预后意义。方法采集159例鼻咽癌患者和159例慢性鼻咽黏膜炎症患者（对照组）的血清和鼻咽组织标本。采用western blotting （WB）和免疫荧光（IF）检测组织样品中EphB2的表达；采用酶联免疫吸附试验（ELISA）测定其血清浓度。生存率差异采用Kaplan-Meier分析和log-rank检验。采用多因素Cox回归分析确定预后相关因素。采用受试者工作特征曲线（ROC）和曲线下面积（AUC）评价EphB2的诊断效能。结果鼻咽癌患者血清和组织标本中tsephb2的表达均明显高于对照组。高水平EphB2与TNM分期、肿瘤侵袭深度、淋巴结转移、远处转移、EBV感染和复发情况显著相关。Kaplan-Meier生存曲线显示，高水平EphB2或EBV（+）或复发的鼻咽癌患者无病生存期最差。Cox回归发现EphB2高表达、EBV（+）和复发是鼻咽癌预后不良的独立预测因素。ROC分析显示，在最佳截断值为7.079 ng/mL时，血清EphB2可有效区分鼻咽癌患者和对照组，AUC为0.904 (95% CI: 0.866-0.942, P < 0.001)，敏感性为79.9%，特异性为98.7%。单独EBV感染的AUC为0.767 (95% CI: 0.714-0.821, P < 0.001)，敏感性为71.1%，特异性为82.4%。联合检测EphB2和EBV感染使AUC提高到0.922 (95% CI: 0.891 ~ 0.954, P < 0.001)，敏感性78.6%，特异性97.5%。结论血清EphB2是鼻咽癌诊断和预后的良好生物标志物。EBV血清阳性和EphB2高表达的结合可能对鼻咽癌早期筛查有价值。
{"title":"Diagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma","authors":"Qiao Huang , Tao Hou , Yi Ren , Wei Xing Liao, Ang Zi Zhu, Ying Liu, Xiao Lin Zhan, Hua Shi Yin","doi":"10.1016/j.tranon.2025.102641","DOIUrl":"10.1016/j.tranon.2025.102641","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC.</div></div><div><h3>Methods</h3><div>Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan–Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).</div></div><div><h3>Results</h3><div>EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan–Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866–0.942, <em>P</em> < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714–0.821, <em>P</em> < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891–0.954, <em>P</em> < 0.001), with 78.6 % sensitivity and 97.5 % specificity.</div></div><div><h3>Conclusions</h3><div>Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102641"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798220","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 : 2026-02-01Epub Date: 2026-01-06DOI: 10.1016/j.tranon.2025.102662
Yihao Liu , Yizhu Gao , Chenyu Huo , Tao Zeng , Wenjun Meng , Haoling Zhang , Qinqin He
Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non-small cell lung cancer (NSCLC) remains a major obstacle and innovative therapeutic approaches are imperative to address it. Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive and long-lasting results in blood cancers, but its success in solid tumors such as lung cancer remains limited. This review summarizes recent advances and future directions of CAR-T therapy in NSCLC, focusing on major therapeutic targets such as EGFR, MSLN, PD-L1, MUC1, CEA, and ROR1, as well as on the efficacy and potential of combining CAR-T therapy with other treatment modalities. Additionally, we discuss adverse events in NSCLC patients undergoing CAR-T therapy, emphasizing cytokine release syndrome (CRS) and cardiovascular complications—their incidence, pathophysiology, interrelation, and management strategies.
{"title":"CAR-T therapy in non-small cell lung cancer: Clinical prospects, potential, and strategies for cardiotoxicity management","authors":"Yihao Liu , Yizhu Gao , Chenyu Huo , Tao Zeng , Wenjun Meng , Haoling Zhang , Qinqin He","doi":"10.1016/j.tranon.2025.102662","DOIUrl":"10.1016/j.tranon.2025.102662","url":null,"abstract":"<div><div>Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non-small cell lung cancer (NSCLC) remains a major obstacle and innovative therapeutic approaches are imperative to address it. Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive and long-lasting results in blood cancers, but its success in solid tumors such as lung cancer remains limited. This review summarizes recent advances and future directions of CAR-T therapy in NSCLC, focusing on major therapeutic targets such as EGFR, MSLN, PD-L1, MUC1, CEA, and ROR1, as well as on the efficacy and potential of combining CAR-T therapy with other treatment modalities. Additionally, we discuss adverse events in NSCLC patients undergoing CAR-T therapy, emphasizing cytokine release syndrome (CRS) and cardiovascular complications—their incidence, pathophysiology, interrelation, and management strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102662"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913238","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 : 2026-02-01Epub Date: 2025-12-17DOI: 10.1016/j.tranon.2025.102637
Shicheng Liu , Qingtao Zhao , Dahu Ren , Lingxin Kong , Hongzhen Zhao , Guochen Duan
{"title":"Corrigendum to “Clinical significance and molecular mechanism of CDX2-CBX3 regulatory axis in lung adenocarcinoma progression” [Transl Oncol. 2025 Nov 10:63:102590]","authors":"Shicheng Liu , Qingtao Zhao , Dahu Ren , Lingxin Kong , Hongzhen Zhao , Guochen Duan","doi":"10.1016/j.tranon.2025.102637","DOIUrl":"10.1016/j.tranon.2025.102637","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102637"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977258","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 : 2026-02-01Epub Date: 2025-12-10DOI: 10.1016/j.tranon.2025.102627
Zhenhao Huang , Jing Luo , Jintong He , Qihui Hu , Rui Liao , Jie Xu , Peng Guo , Zhipeng Liu , Nan You , Baoyong Zhou , Rui Tao
Background
Gallbladder cancer (GBC) has poor prognosis, and reliable preoperative biomarkers remain limited. Systemic inflammation-based indices, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), may predict outcomes, but their comparative value and association with TNM stage are unclear.
Methods
This multicenter retrospective study included 210 patients who underwent curative-intent resection for GBC (2015–2023). Preoperative SII, NLR, and MLR were calculated from peripheral blood counts. Prognostic performance was evaluated by time-dependent ROC, Kaplan–Meier, and Cox regression analyses. Restricted cubic spline models assessed non-linear associations. Associations with TNM stage were analyzed using the Jonckheere–Terpstra trend test, and stratified survival analysis was conducted.
Results
SII showed the highest predictive accuracy for overall survival (OS, AUC = 0.745) and recurrence-free survival (RFS, AUC = 0.689), outperforming NLR and MLR. In multivariable analysis, only elevated SII independently predicted poorer OS (HR = 4.601, 95% CI: 1.178–17.965, P = 0.028). Restricted cubic spline revealed an “S-shaped” non-linear relationship between SII and OS risk and a linear association with RFS. SII levels significantly increased with advancing TNM stage (P = 0.042) and provided superior prognostic stratification in advanced disease, while NLR and MLR showed weaker stage-related trends.
Conclusions
Among SII, NLR, and MLR, preoperative SII showed comparatively stronger and more consistent associations within this retrospective multicenter cohort. SII independently predicted OS, correlated with TNM stage, and appeared to offer better stratification in advanced disease. As a simple and readily available biomarker, SII may be considered to complement TNM staging for preoperative risk assessment; however, these findings should be interpreted cautiously and require confirmation in prospective multicenter studies.
{"title":"Comparative prognostic value of preoperative SII, NLR, and MLR and their association with TNM staging in gallbladder cancer: A multicenter retrospective study","authors":"Zhenhao Huang , Jing Luo , Jintong He , Qihui Hu , Rui Liao , Jie Xu , Peng Guo , Zhipeng Liu , Nan You , Baoyong Zhou , Rui Tao","doi":"10.1016/j.tranon.2025.102627","DOIUrl":"10.1016/j.tranon.2025.102627","url":null,"abstract":"<div><h3>Background</h3><div>Gallbladder cancer (GBC) has poor prognosis, and reliable preoperative biomarkers remain limited. Systemic inflammation-based indices, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), may predict outcomes, but their comparative value and association with TNM stage are unclear.</div></div><div><h3>Methods</h3><div>This multicenter retrospective study included 210 patients who underwent curative-intent resection for GBC (2015–2023). Preoperative SII, NLR, and MLR were calculated from peripheral blood counts. Prognostic performance was evaluated by time-dependent ROC, Kaplan–Meier, and Cox regression analyses. Restricted cubic spline models assessed non-linear associations. Associations with TNM stage were analyzed using the Jonckheere–Terpstra trend test, and stratified survival analysis was conducted.</div></div><div><h3>Results</h3><div>SII showed the highest predictive accuracy for overall survival (OS, AUC = 0.745) and recurrence-free survival (RFS, AUC = 0.689), outperforming NLR and MLR. In multivariable analysis, only elevated SII independently predicted poorer OS (HR = 4.601, 95% CI: 1.178–17.965, <em>P</em> = 0.028). Restricted cubic spline revealed an “S-shaped” non-linear relationship between SII and OS risk and a linear association with RFS. SII levels significantly increased with advancing TNM stage (<em>P</em> = 0.042) and provided superior prognostic stratification in advanced disease, while NLR and MLR showed weaker stage-related trends.</div></div><div><h3>Conclusions</h3><div>Among SII, NLR, and MLR, preoperative SII showed comparatively stronger and more consistent associations within this retrospective multicenter cohort. SII independently predicted OS, correlated with TNM stage, and appeared to offer better stratification in advanced disease. As a simple and readily available biomarker, SII may be considered to complement TNM staging for preoperative risk assessment; however, these findings should be interpreted cautiously and require confirmation in prospective multicenter studies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102627"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705249","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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