Translational Oncology最新文献

{"title":"Corrigendum to “A Clinical Study on the Efficacy of Concurrent Chemoradiotherapy Combined with Targeted Therapy and Hyperthermia in Patients with Locally Advanced Cervical Cancer” [Translational Oncology,Volume61, November 2025, 102516]","authors":"Yuhan Jia , Feng Zhang , Kun Zou , Lijuan Zou","doi":"10.1016/j.tranon.2025.102656","DOIUrl":"10.1016/j.tranon.2025.102656","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102656"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977259","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}

{"title":"NTRK2 promotes malignant progression and paclitaxel resistance of lung adenocarcinoma through targeting MYC/ABCF1 axis","authors":"Rongrong Cui ,&nbsp;Yuanyuan Wang ,&nbsp;Yao Yao ,&nbsp;Xiaojuan Ren ,&nbsp;Yuchen Zhang ,&nbsp;Daxu Li ,&nbsp;Peng Hou ,&nbsp;Meiju Ji ,&nbsp;Yiping Qu","doi":"10.1016/j.tranon.2025.102655","DOIUrl":"10.1016/j.tranon.2025.102655","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, and the development of chemoresistance often leads to tumor recurrence and metastasis. Neurotrophic receptor tyrosine kinase 2 (NTRK2) has been implicated in tumorigenesis and chemotherapy resistance, but its precise role in LUAD and contribution to paclitaxel resistance remain unclear. In this study, we found that NTRK2 expression was significantly upregulated in LUADs compared with paired noncancerous tissues and was further elevated in samples from patients who experienced recurrence following paclitaxel-based chemotherapy. Functional assays demonstrated that <em>NTRK2</em> knockdown markedly inhibited the malignant phenotypes of LUAD cells <em>in vitro</em> and significantly restored the sensitivity of LUAD cells to paclitaxel. Conversely, <em>NTRK2</em> overexpression promoted cell proliferation, colony formation, and reduced responsiveness to paclitaxel. Consistently, <em>in vivo</em> xenograft experiments revealed that <em>NTRK2</em> knockdown suppressed tumor growth and enhanced the antitumor efficacy of paclitaxel. Mechanistically, NTRK2 activated the MAPK/ERK and PI3K/AKT signaling pathways, leading to the upregulation of MYC, which in turn directly activated the transcription of ATP-binding cassette subfamily F member 1 (<em>ABCF1</em>), thereby promoting LUAD progression and paclitaxel resistance. Collectively, our findings identify NTRK2 as a critical oncogenic driver that confers chemoresistance by activating the NTRK2/MYC/ABCF1 signaling axis. This study provides new mechanistic insights into the regulation of paclitaxel resistance in LUAD and highlights NTRK2 and its downstream effectors as promising therapeutic targets for overcoming chemoresistance.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102655"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912842","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}

{"title":"Interleukin 35 promotes progression of hepatocellular carcinoma by recruiting neutrophils","authors":"Wei Gan ,&nbsp;Guo-Qiang Sun ,&nbsp;Jin-Long Huang ,&nbsp;Bao-Ye Sun ,&nbsp;Zhu-Tao Wang ,&nbsp;Zhang-Fu Yang ,&nbsp;Cheng Zhou ,&nbsp;Yong Yi ,&nbsp;Shuang-Jian Qiu","doi":"10.1016/j.tranon.2025.102630","DOIUrl":"10.1016/j.tranon.2025.102630","url":null,"abstract":"<div><h3>Background</h3><div>A growing number of therapeutic strategies against hepatocellular carcinoma (HCC) have emerged. However, their efficacy remains limited. This study investigated the mechanism of interleukin-35 (IL-35) in the progression of HCC and its potential application in HCC treatment.</div></div><div><h3>Methods</h3><div>The expression of IL-35,Gp130 ,IL12-Rβ2, CCL3,etc. in HCC tissues was detected by immunohistochemistry(IHC), and the expression of IL-35 in HCC cell lines was detected by fluorescence assay. Kaplan-Meier survival analysis of IL-35 and its receptor in relation to overall survival(OS) and recurrence free survival(RFS) in patients with HCC. The mouse subcutaneous tumor models to study the effects of IL-35 on HCC growth and immune cells. Western blot were used to detect the expression IL-35, CCL3, FGF2, and flow cytometric plot were performed to explore the immune cells infiltration in the tumor tissue.</div></div><div><h3>Results</h3><div>High expression of IL-35 in patients with HCC was associated with poor prognosis. Furthermore, IL-35 could facilitate tumor progression by affecting neutrophil infiltration, angiogenesis, and CD8+ T-cell infiltration. Additionally, CCL3 was a key factor mediating the recruitment of neutrophils by IL-35. FGF2 derived from neutrophils stimulated by IL-35 promoted intratumoral angiogenesis. IL-35 also facilitated the adhesion of tumors to endothelial cells, with neutrophils further enhancing this effect both. Anti-IL-35 antibody combined with anti-PD1 antibody significantly enhanced which therapeutic effect in HCC.</div></div><div><h3>Conclusions</h3><div>Our data show that the high expression of IL-35 in patients with HCC is an important tumor promoter. Combined treatment with anti-IL-35 and anti-PD1 antibodies have potential therapeutic effect against HCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102630"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912731","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}

{"title":"Single‑cell mapping of neutrophil extracellular trap signatures in lung adenocarcinoma reveals immune landscapes, prognostic potential, and therapeutic targets","authors":"Jingjie Liu ,&nbsp;Kang Tian ,&nbsp;Hui Shen ,&nbsp;Lei Zhou ,&nbsp;Subo Dong ,&nbsp;Fuchun Huo ,&nbsp;Jian Zhang","doi":"10.1016/j.tranon.2025.102651","DOIUrl":"10.1016/j.tranon.2025.102651","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) have emerged as key modulators in the tumor microenvironment, yet their cellular heterogeneity, molecular mechanisms, and clinical relevance in lung adenocarcinoma (LUAD) remain elusive. Here, we performed an integrative single‑cell and multi‑omics dissection of NETs activity across LUAD tissues. Single‑cell transcriptomics revealed that NETs signatures were predominantly enriched in neutrophils but also detectable in dendritic cells and macrophages, where NETs‑high subpopulations exhibited intensified intercellular signaling. Genomic profiling indicated that NETs‑related genes were largely affected by missense mutations and single nucleotide polymorphisms (C &gt; A and C &gt; T), with frequent alterations in PTPRD, VCAN, and ZNF804A. Functional enrichment associated these genes with immune regulation and tumor‑promoting pathways. By integrating seven independent clinical cohorts, we constructed a machine‑learning–based NETs‑related prognostic signature (NETs‑Sig) that robustly predicted overall survival across datasets (AUC &gt; 0.75). Patients with high NETs‑Sig scores exhibited immune‑cold phenotypes characterized by reduced immune infiltration and impaired antigen presentation, whereas low‑score cases displayed elevated MHC‑II expression, enhanced antigen processing, and putative sensitivity to immunotherapy. Experimental validation further identified AP2S1 as a central NETs‑Sig gene—overexpressed in multiple cancers and functionally promoting invasion and metastasis in LUAD cells. Together, our study delineates the cellular, genomic, and immunological frameworks of NETs in LUAD, establishes NETs‑Sig as a clinically actionable biomarker for risk stratification and immunotherapy guidance, and highlights AP2S1 as a promising therapeutic target for translational intervention.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102651"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913036","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}

{"title":"Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSR+AEC in clear cell renal cell carcinoma","authors":"Haixiang Zhang ,&nbsp;Jiafeng Hou ,&nbsp;Long Zhang ,&nbsp;Peng Luo ,&nbsp;Hanzhong Zhang ,&nbsp;Aiming Jiang ,&nbsp;Xuebing Ren ,&nbsp;Chunbiao Wu","doi":"10.1016/j.tranon.2025.102650","DOIUrl":"10.1016/j.tranon.2025.102650","url":null,"abstract":"<div><h3>Background</h3><div>Bone metastasis is a common and lethal complication of advanced clear cell renal cell carcinoma (ccRCC), yet the cellular and spatial architecture of the human bone metastatic niche remains incompletely defined, limiting identification of actionable targets.</div></div><div><h3>Methods</h3><div>We integrated matched single cell RNA sequencing with spatial transcriptomics and large scale bulk cohorts. Integrating multi computational pipelines to derive and validate an INSR⁺ artery endothelial relevant prognostic signature (IAERS). Functional consequences of <em>COL4A1</em> were assessed with in vitro experiments.</div></div><div><h3>Results</h3><div>Single cell and spatial analyses uncovered pronounced malignant cell heterogeneity and a metastatic malignant programme enriched for extracellular matrix and adhesion pathways. Endothelial cells displayed the strongest inferred crosstalk with metastatic tumour cells; an INSR⁺ AEC subset was selectively enriched in bone metastases and spatially colocalized with metastatic foci. Ligand-receptor modelling identified a dominant <em>COL4A1</em>-<em>SDC4</em> signalling axis linking INSR⁺ AEC to metastatic tumo ur cells, and GeneSwitches nominated <em>TCF4</em> as a transcriptional switch sustaining the INSR⁺ AEC programme. <em>COL4A1</em> knockdown impaired ccRCC proliferation, migration and invasion in vitro. A novel IAERS signature derived from INSR⁺ AEC programmes robustly stratified patient survival and metastatic status across independent cohorts.</div></div><div><h3>Conclusions</h3><div>These multi‑modal data define a prometastatic vascular niche in ccRCC centred on <em>TCF4</em> associated INSR⁺ AEC and a <em>COL4A1</em>-<em>SDC4</em> axis, providing candidate biomarkers and therapeutic avenues that target endothelial matrix interactions in bone metastatic disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102650"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774486","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}

{"title":"Mechanistic and translational insights into plant-derived natural products in preclinical multiple myeloma research: Current evidence","authors":"Lulu Li ,&nbsp;Jie Xu ,&nbsp;Liming Yu ,&nbsp;Jingbo Shi ,&nbsp;Changnian Li ,&nbsp;Jiabao Gu ,&nbsp;Yaru Wang ,&nbsp;Siyuan Cui","doi":"10.1016/j.tranon.2026.102666","DOIUrl":"10.1016/j.tranon.2026.102666","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chimeric antigen receptor T-cell (CAR-T) therapy, relapse and drug resistance remain major challenges that urgently need to be addressed. Plant-derived natural products have attracted increasing attention in recent years due to their multi-target synergistic effects, demonstrating unique potential in inducing MM cell apoptosis, reversing drug resistance, and modulating the immune microenvironment—making them a rising focus in translational medicine research. In this structured narrative review, we systematically summarize the anti-myeloma mechanisms of fourteen plant-derived natural products, including plant-derived monomeric compounds (baicalein, artemisinin, curcumin, celastrol, gambogic acid, resveratrol, ginsenosides, icariin, oridonin, plumbagin, formononetin) and standardized plant extracts (<em>Strychnos nux-vomica</em> root extract, dandelion flavonoids, <em>Hedyotis diffusa</em> polysaccharides). This review highlights their multi-target regulatory effects on signaling pathways, cell cycle modulation, and immune regulation, and further discusses their potential translational value in overcoming drug resistance and optimizing combination treatment strategies. Literature was retrieved from PubMed, Web of Science, and CNKI databases, covering studies published up to January 2025. Although plant-derived natural products exhibit promising multi-target regulatory mechanisms in MM therapy, their clinical translation remains limited by poor bioavailability of single compounds and the lack of standardized extracts. Future research should integrate systems pharmacology with clinical studies to elucidate multi-component synergistic networks and develop novel targeted formulations, thereby accelerating the efficient translation of phytochemicals from bench to bedside.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102666"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939212","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}

{"title":"A serum-derived 3D tumor model platform for personalized prediction and monitoring of chemotherapeutic response in pancreatic ductal adenocarcinoma","authors":"Sara Cherradi ,&nbsp;Salomé Roux ,&nbsp;Marie Dupuy ,&nbsp;Eric Assenat ,&nbsp;Hong Tuan Duong","doi":"10.1016/j.tranon.2025.102659","DOIUrl":"10.1016/j.tranon.2025.102659","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLFIRINOX and gemcitabine-based therapies offer some benefit, treatment selection remains empirical, with no reliable predictive models to guide personalized decisions. We adapted our previously validated serum-derived educated spheroid technology creating 3D spheroids using PDAC patient serum. These spheroids maintained structural integrity, viability, and consistent size over eight days, avoiding overgrowth. They also exhibited extracellular matrix deposition such as type I collagen, and expressed key genes involved in drug resistance and tumor progression including <em>COL1A1, FN1, MMP2, CXCL1</em>, and <em>CXCL2</em>. Using the Target-Independent Cell Killing (TICK) strategy, we established individualized chemograms to assess true therapeutic response helping clinicians in refining the optimal treatment protocol. In a 16-case study, our model achieved high concordance with clinical responses across gemcitabine, Gem-Pac, and FOLFIRINOX treatments supporting its utility in personalized care. Finally, we demonstrated that predictive accuracy was highest when patient serum was collected within a short window prior to treatment initiation. These findings support PDAC patient serum-educated spheroids as a rapid, non-invasive, and physiologically relevant tool for guiding personalized chemotherapy and monitoring treatment response in real time.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102659"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913218","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}

{"title":"Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma","authors":"Jinna Tan ,&nbsp;Junzhu Liang ,&nbsp;Yaoyang Li ,&nbsp;Jiaqian He ,&nbsp;Hui Yin ,&nbsp;Hemeng Wu ,&nbsp;Yuzhen Luo ,&nbsp;Mingfen Li ,&nbsp;Fuli Long ,&nbsp;Hongsheng Lin","doi":"10.1016/j.tranon.2025.102663","DOIUrl":"10.1016/j.tranon.2025.102663","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear.</div></div><div><h3>Methods</h3><div>Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115) and spatial transcriptomics were integrated; function was tested by RPL8 knockdown, proliferation/migration assays and drug-sensitivity screens.</div></div><div><h3>Results</h3><div>RPL8 mRNA/protein were markedly elevated (<em>p</em> &lt; 0.001) with AUC 0.95 for diagnosis. High RPL8 independently predicted shorter overall (HR 1.42) and disease-specific survival (HR 1.35). Mechanistically, RPL8 co-activated MYC/G2M signaling, rewired glutathione metabolism and correlated with cell-cycle/DNA-repair scores (<em>p</em> &lt; 0.001). scRNA-seq showed selective RPL8 enrichment in malignant hepatocytes and exhausted CD8⁺ <em>T</em> cells; spatial maps revealed tumor-confined expression inversely linked to immune infiltration (<em>p</em> &lt; 0.01). Silencing RPL8 suppressed proliferation, migration and glutathione synthesis (<em>p</em> &lt; 0.001), while sensitizing cells to sirolimus and sclareol (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>RPL8 drives HCC progression and immune evasion, qualifying it as a diagnostic biomarker and therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102663"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913204","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}

{"title":"MAZ-Mediated ubiquitin-conjugating enzyme E2C upregulation promotes breast cancer progression via the MAPK signaling pathway","authors":"Jinhui Bai ,&nbsp;Mei Deng ,&nbsp;Xueting Wu ,&nbsp;Chao Xiong ,&nbsp;Huixian Wu ,&nbsp;Li Wang ,&nbsp;Jie Qin","doi":"10.1016/j.tranon.2025.102646","DOIUrl":"10.1016/j.tranon.2025.102646","url":null,"abstract":"<div><h3>Background</h3><div>Malignant proliferation and invasion of tumor cells are the primary causes of death among patients with breast cancer, yet the molecular mechanisms orchestrating cancer metastasis are not well elucidated. Ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be involved in the tumorigenesis and development of various malignant tumors; however, the biological roles and underlying mechanisms of UBE2C in breast cancer remain unclear.</div></div><div><h3>Methods</h3><div>UBE2C expression was analyzed in breast cancer tissue and cell lines using immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR) and Western blot. The biological roles of UBE2C and its transcription factor MAZ were investigated in vitro using CCK-8, plate cloning, scratch, Transwell, cell cycle and apoptosis assays, while a nude mouse subcutaneous tumorigenic model was employed for the in vivo studies. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to validate the binding relationship between MAZ and UBE2C.</div></div><div><h3>Results</h3><div>UBE2C expression is elevated in breast cancer, and higher levels of UBE2C are associated with poorer survival among patients with breast cancer. UBE2C promotes the progression of breast cancer both in vivo and in vitro. Additionally, UBE2C is a direct transcriptional target of MAZ, which also accelerates malignant development of breast cancer. Furthermore, UBE2C exerts its oncogenic effects dependent on the MAPK signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the critical role of the MAZ/UBE2C/MAPK signaling axis in the progression of breast cancer and identify potential novel therapeutic targets for its treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102646"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912712","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}

{"title":"Single-cell analysis identifies a stemness-associated tumor cell subpopulation and develops a prognostic scoring model in esophageal squamous cell carcinoma","authors":"Wei Ye ,&nbsp;Wei Su ,&nbsp;Chang Lei ,&nbsp;Chenjun Huang ,&nbsp;Mingjun Du","doi":"10.1016/j.tranon.2025.102653","DOIUrl":"10.1016/j.tranon.2025.102653","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumor subpopulations in ESCC, among which one cluster displayed prominent stem‑like and proliferative features with high expression of MKI67, STMN1, and UBE2C. Based on its marker genes, we established a stemness‑associated scoring model (SASM). Validation in independent TCGA and GSE53624 cohorts confirmed that higher SASM scores predicted shorter overall survival and reduced immune infiltration, particularly of CD8⁺ T cells. SASM scores were positively correlated with tumor mutational burden (TMB), and patients with high SASM and low TMB exhibited the poorest outcomes. Further analysis identified TFDP1 as a key gene associated with SASM and adverse prognosis, which was upregulated in tumor tissues and promoted ESCC cell proliferation in vitro. Overall, our study delineates stemness‑related tumor heterogeneity in ESCC, proposes a prognostic scoring system with immunological relevance, and highlights TFDP1 as a potential therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102653"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913003","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}