Translational Oncology最新文献

{"title":"Construction and validation of an ACTA2-based prognostic scoring model for colorectal adenocarcinoma","authors":"Xiao Che ,&nbsp;Wenwei Huang ,&nbsp;Yao Ying ,&nbsp;Yuzhen Zhu ,&nbsp;Yang Yang ,&nbsp;Ke Mo ,&nbsp;Xueqiong Han ,&nbsp;Chunhui Cui ,&nbsp;Lu Zhou","doi":"10.1016/j.tranon.2025.102530","DOIUrl":"10.1016/j.tranon.2025.102530","url":null,"abstract":"<div><div>This study aimed to construct and validate a clinical scoring model for colorectal adenocarcinoma (COAD) based on ACTA2 to identify novel biomarkers. COAD-related data were obtained from the TCGA database, and the expression of ACTA2 was verified by in vitro experiments. WGCNA analysis was used to explore the biological processes associated with ACTA2. The results showed that ACTA2 was downregulated in COAD tissues, but its high expression was significantly associated with poor prognosis in patients. ACTA2 was closely related to immune cell infiltration, immune checkpoint genes, and tertiary lymphoid structure marker genes. In addition, there was a negative correlation between the methylation level and transcriptional level of ACTA2. The ACTA2-based clinical scoring model constructed in this study may serve as a novel biomarker for COAD, providing new insights for improving patient prognosis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102530"},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087496","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":"Development of a translational radiobiology platform using pancreatic cancer patient-derived organoids for personalized radiation oncology","authors":"Christopher Kessler ,&nbsp;Francheska Cadacio ,&nbsp;Carlo Maurer ,&nbsp;Arlett Schäfer ,&nbsp;Felix Orben ,&nbsp;Julius C. Fischer ,&nbsp;Daniela Schilling ,&nbsp;Lisa Fricke ,&nbsp;Sebastian Rasch ,&nbsp;Ihsan E. Demir ,&nbsp;Katja Steiger ,&nbsp;Wilko Weichert ,&nbsp;Roland M. Schmid ,&nbsp;Stephanie E. Combs ,&nbsp;Maximilian Reichert ,&nbsp;Sophie Dobiasch","doi":"10.1016/j.tranon.2025.102535","DOIUrl":"10.1016/j.tranon.2025.102535","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with neoadjuvant radio(chemo)therapy failing in approximately 70 % of cases due to high tumor heterogeneity, and intrinsic radioresistance. Patient-derived organoids (PDOs) closely recapitulate appearance, and functionality as the original tissue and have potential to explore novel therapies for personalized radiooncology.</div><div>In this study, the radioresponse of PDAC PDO lines was determined after irradiation (RT). PDOs were immunohistochemically characterized by γ-H2AX, HIF-1α and Ki-67 staining. RNA sequencing data were analyzed by gene set enrichment analyses to investigate underlying mechanisms of radioresistance. Preclinical findings were correlated with clinical data from the corresponding patients.</div><div>PDOs showed a significant heterogeneity in response to radiation and were classified into radiosensitive, intermediate, and radioresistant subgroups. A correlation between radiosensitivity and enhanced proliferation and decreased hypoxia was observed. OXPHOS-related gene signatures were significantly overexpressed in the radioresistant phenotype. Translationally, radioresistance in PDOs was associated with significantly poorer survival of patients.</div><div>Our platform demonstrated heterogeneity in radioresponse reflecting the clinical situation and correlation with clinical outcomes. Immunohistochemical staining and transcriptomic profiling identified molecular signatures, including HIF-1α and OXPHOS-related pathways, associated with radioresistance. Implementing PDO-based radioresponse profiling in clinical workflows may enable patient stratified treatment approaches. Overall, our findings suggest that functionalizing PDOs for radioresponse might extend PDO-informed precision oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102535"},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087546","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":"Dioscin initiates dual roles in bladder cancer progression via miR-195–5p/FASN/SLC3A2 axis-mediated cell death mechanisms","authors":"Yongchang Lai ,&nbsp;Zhenping Peng ,&nbsp;Zhaohui He ,&nbsp;Zechao Lu ,&nbsp;Shudan Yan ,&nbsp;Qihong Nie ,&nbsp;Yuke Xiang","doi":"10.1016/j.tranon.2025.102534","DOIUrl":"10.1016/j.tranon.2025.102534","url":null,"abstract":"<div><div>Emerging evidence highlights dioscin, a bioactive compound derived from Dioscoreaceae plants, as a promising antitumor agent, yet its regulatory mechanisms in bladder cancer and interaction with microRNAs remain unclear. This study systematically investigated dioscin's dual roles in bladder cancer progression through <em>in vitro</em> and <em>in vivo</em> models. Functional assays demonstrated that dioscin significantly upregulated miR-195–5p expression in bladder cancer cells, while both dioscin and miR-195–5p suppressed T24/EJ cell proliferation, migration, and invasion. Mechanistically, RNA-seq and molecular docking revealed dioscin directly bound to fatty acid synthase (FASN), which then regulated the SLC3A2 expression. Strikingly, miR-195–5p mimic transfection downregulated FASN, whereas its inhibitor reversed this effect, confirming miR-195–5p's pivotal role in dioscin-mediated FASN/SLC3A2 inhibition. Notably, dioscin potentiated cisplatin's antitumor efficacy against both BIU87 and cisplatin-resistant BIU87 bladder cancer cells at low micromolar concentrations. Intriguingly, the bladder cancer cell induced by dioscin could be counteracted by inhibitors of apoptosis, necroptosis, and ferroptosis, particularly in the presence of gap junction inhibitor carbenoxolone. However, <em>in vivo</em> studies uncovered a paradoxical duality: dioscin enhanced N-methyl-N-nitrosourea (MNU)-induced bladder tumorigenesis. Its combination with MNU exacerbated renal toxicity and bladder stone formation in rats, accompanied by elevated creatinine and uric acid levels. Crucially, dioscin exhibited cytotoxicity against normal urothelial (SV-HUC-1) and renal (MDCK) cells, warranting cautious therapeutic application. These findings unveil a novel miR-195–5p/FASN/SLC3A2 axis through which dioscin initiates bladder cancer cell death, while highlighting dual roles of dioscin in bladder cancer and the necessity for dosage optimization to balance its antitumor potency and off-target toxicity.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102534"},"PeriodicalIF":5.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081592","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 CEBPB/TYMP/GDF15 signaling axis mediates tumor growth and cisplatin resistance in bladder cancer","authors":"Shuo Tian ,&nbsp;Chuang Wang ,&nbsp;Xupeng Zhao ,&nbsp;Yundong Xuan ,&nbsp;Wenjie Wei ,&nbsp;Yuhao Dong ,&nbsp;Wen Tao ,&nbsp;Chi Zhang ,&nbsp;Tianwei Cai ,&nbsp;Chunyu Liu ,&nbsp;Yan Huang ,&nbsp;Xu Zhang","doi":"10.1016/j.tranon.2025.102537","DOIUrl":"10.1016/j.tranon.2025.102537","url":null,"abstract":"<div><div>Cisplatin-based chemotherapy remains the standard treatment for muscle-invasive bladder cancer (BC), yet resistance significantly limits its long-term efficacy. Reliable biomarkers for prognosis and therapeutic guidance are also lacking. Here, we identify thymidine phosphorylase (TYMP) as an independent prognostic risk factor that promotes BC progression and mediates cisplatin resistance. Bioinformatic analyses of TCGA and GEO datasets revealed elevated TYMP expression in BC tissues, correlating with poor patient outcomes. Functional studies in UMUC3, T24, and MB49 cell lines, as well as in syngeneic mouse models, demonstrated that TYMP knockdown suppressed BC cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), while enhancing cisplatin sensitivity. Pharmacological inhibition of TYMP using TAS-102 significantly augmented cisplatin-induced cytotoxicity in vivo. Mechanistically, the transcription factor CEBPB directly bound to and activated the TYMP promoter, thereby upregulating GDF15 expression and driving tumor growth and chemoresistance. TYMP expression positively correlated with both CEBPB and GDF15 levels in public datasets. Collectively, our findings define a CEBPB/TYMP/GDF15 signaling axis that fosters BC progression and cisplatin resistance and highlight TYMP as a novel prognostic biomarker and potential therapeutic target, with TAS-102 offering a promising strategy for overcoming cisplatin resistance.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102537"},"PeriodicalIF":5.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060140","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":"Curcumin suppresses colorectal cancer by inhibiting TRIM2 and mTOR signaling","authors":"Hang Yu ,&nbsp;Haikuo Wu ,&nbsp;Qianhui Zhao ,&nbsp;Ruitao Zhao ,&nbsp;Jian Liu ,&nbsp;Zhiyuan Yang ,&nbsp;Wang Song ,&nbsp;Yudong Li","doi":"10.1016/j.tranon.2025.102517","DOIUrl":"10.1016/j.tranon.2025.102517","url":null,"abstract":"<div><div>Curcumin, a natural polyphenol, exhibits potent anti-cancer activities, but its underlying molecular mechanisms in colorectal cancer (CRC) are not fully elucidated. Here, we investigated t whether curcumin suppresses CRC by targeting tripartite motif-containing protein 2 (TRIM2) and its downstream the Mammalian Target of Rapamycin (mTOR) signaling pathway. We initially performed a whole-genome expression profile chip to examine gene alterations following curcumin administration. Our results demonstrate that curcumin effectively decreased the expression of TRIM2 in CRC cells. Furthermore, PCR and immunohistochemical (IHC) staining of tumour samples confirmed the elevated expression of TRIM2 in CRC cells and CRC tumour samples. Additionally, we assessed the effect of TRIM2 knockdown on the proliferation of CRC cells and tumour growth using cell and animal experiments. mTOR pathway activity was interrogated using phospho‑kinase arrays and immunoblotting, with pharmacologic rescue by an mTOR activator. Our findings revealed that curcumin administration and TRIM2 knockdown effectively suppressed the migration and proliferation of CRC cells and mTOR activation partially reversed these effects, Mechanistically, TRIM2 depletion dampened mTOR signaling, reducing phosphorylation of AKT (Ser473), and S6K/4EBP1 without altering total protein levels. These findings indicate curcumin inhibits CRC onset and progression by downregulating TRIM2 and suppressing mTOR pathway activity, suggesting TRIM2 may serve as a potential prognostic marker in CRC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102517"},"PeriodicalIF":5.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049262","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":"Personalizing colorectal Cancer treatment: Chemotherapy drug testing with patient-derived tumor cell clusters","authors":"Xiaoyuan Qiu ,&nbsp;Ruiqiang Li ,&nbsp;Jiaolin Zhou ,&nbsp;Peng Li ,&nbsp;Gengchen Xie ,&nbsp;Shenyi Yin ,&nbsp;Leilei Yang ,&nbsp;Guole Lin","doi":"10.1016/j.tranon.2025.102518","DOIUrl":"10.1016/j.tranon.2025.102518","url":null,"abstract":"<div><h3>Background</h3><div>Due to the heterogeneity of colorectal cancer (CRC), models that can predict the chemotherapy response are needed to facilitate personalized treatment.</div></div><div><h3>Aim</h3><div>To construct patient-derived tumor-like cell cluster (PTC) models in vitro drug sensitivity screening for CRC personalized chemotherapy.</div></div><div><h3>Methods</h3><div>We collected 140 CRC tissues via surgical resection in three Chinese hospitals and establish PTC models which is highly similar to the original tumor tissue. The sensitivity to various chemotherapy drugs was assessed in these PTC models. We recorded the PTC model cultivation process and patients' clinical data and assessed the concordance between in vitro drug sensitivity and clinical outcomes.</div></div><div><h3>Results</h3><div>PTC models were successfully established from 124 specimens, with a success rate of 88.6 %. The average culture time was 3.02 ± 1.56 days, and the median time to obtain drug sensitivity results was 11 days (10–13 days). Drug sensitivity testing revealed that the PTC models had variable responses to different chemotherapy regimens, with some patients showing unexpected sensitivity to regimens not typically considered first-line treatments. The median follow-up time for all patients was 19 months, and there was no significant difference in disease-free survival (DFS) between patients whose actual responses to clinical treatment regimens were consistent or inconsistent with the PTC model predictions.</div></div><div><h3>Conclusion</h3><div>The PTC model for drug sensitivity testing has advantages of high success rate and rapid drug screening time. This study provides a promising tool for personalized chemotherapy sensitivity screening in patients with CRC and, after further clinical trials, may guide clinical treatment decision making.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102518"},"PeriodicalIF":5.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048461","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":"Patient-derived extracellular matrix from decellularized high-grade serous ovarian carcinoma tissues as a biocompatible support for organoid growth","authors":"Francesca Sensi ,&nbsp;Giulia Spagnol ,&nbsp;Ombretta Repetto ,&nbsp;Edoardo D'Angelo ,&nbsp;Andrea Biccari ,&nbsp;Asia Marangio ,&nbsp;Angela Guerriero ,&nbsp;Astrid A. Mollo Castillo ,&nbsp;Andrea Vogliardi ,&nbsp;Eleonora Zanrè ,&nbsp;Elisa Cimetta ,&nbsp;Francesca Schiavi ,&nbsp;Filippo Sperti ,&nbsp;Matteo Marchetti ,&nbsp;Orazio de Tommasi ,&nbsp;Marco Noventa ,&nbsp;Carlo Saccardi ,&nbsp;Gaya Spolverato ,&nbsp;Roberto Tozzi ,&nbsp;Marco Agostini","doi":"10.1016/j.tranon.2025.102523","DOIUrl":"10.1016/j.tranon.2025.102523","url":null,"abstract":"<div><div>High-grade serous ovarian cancer (HGSOC) is the most common clinically diagnosed ovarian cancer, often considered a fatal disease. Although current treatments appear to provide almost complete remission, the recurrence rate is still high. Here we present an innovative tissue engineering approach applied to HGSOC by combining patient-derived decellularized extracellular matrix (dECM) and patient-derived organoids (PDO), intending to provide a three-dimensional (3D) model useful to evaluate treatment response. By histology, immunohistochemistry, immunofluorescence, and second harmonic generation microscopy, we demonstrated that dECM maintains the structural environment of native tumoral tissue. Proteomic analysis performed on isolated dECM compared to the native tumor revealed a dominant set of functionally related proteins associated with ECM assembly, organization and morphology consistent with preservation of a tissue-specific niche for later PDO seeding and infiltration. In parallel, we established a protocol for the PDO derivation with an initiation efficiency of 83.3 %. We compared PDO with its native tumor counterpart using diagnostics markers with a concordance index of 100 % for CK7 and P16 and 66 % for P53mut, PAX8 and WT1. The IC50 concentrations of PDO treated with Paclitaxel and Paclitaxel plus Carboplatin resulted in 37.10 µM and 6.8 µM, respectively, after treatment. The dECM recellularized by injection with PDO, and treated with drugs displayed a reduced sensitivity to standard first-line chemotherapy. This 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays.</div></div><div><h3>Novelty and Impact statement</h3><div>The novelty of this research lies in the fact that, for the first time, a three-dimensional preclinical model of ovarian cancer fully derived from the patient has been generated. The patient's decellularized extracellular matrix is capable of supporting the growth of organoids and produces a response to chemotherapy treatment that more closely resembles the actual doses used in vivo compared to organoids grown solely in commercial matrices. We hope that the presented model can have a useful impact in identifying the right drugs to treat patients, and avoiding unnecessary toxicity.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102523"},"PeriodicalIF":5.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048462","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":"KRAS mutations promote PD-L1-mediated immune escape by ETV4 in lung adenocarcinoma","authors":"Daqi Jia,&nbsp;Peng Wang,&nbsp;Shiqi Zheng,&nbsp;Zi Lei,&nbsp;Wenmang Xu,&nbsp;Yuanyuan Wang,&nbsp;Xinyan Pan,&nbsp;Qiang Feng,&nbsp;Julun Yang","doi":"10.1016/j.tranon.2025.102525","DOIUrl":"10.1016/j.tranon.2025.102525","url":null,"abstract":"<div><div>KRAS mutations are frequently associated with immune escape in lung adenocarcinoma. The aim of this research is to investigate the molecular mechanism underlying the KRAS-driven upregulation of PD-L1 and its role in immune escape. Methods: Transcriptomic data combined with data from the GEO database and immunohistochemistry were used to analyze the expression of PD-L1 in KRAS-mutant tissues. Functional experiments were performed using KRAS knockdown and MEK-ERK signaling pathway inhibitors to reveal the major signaling pathways by which KRAS mutations regulate PD-L1 expression. The key transcription factors regulating PD-L1 expression were identified through weighted gene coexpression network analysis (WGCNA) combined with dataset screening, and the binding sites of the key transcription factors to the PD-L1 promoter region were predicted using the JASPAR database and verified by luciferase reporting experiments and ChIP experiments. Flow cytometry, LDH assays, graft tumor assays, multicolor immunofluorescence and immunohistochemistry were used to determine whether key transcription factors affected PD-L1-mediated immune escape in KRAS-mutated lung adenocarcinoma. Results: PD-L1 expression was markedly increased in KRAS-mutant lung adenocarcinoma, and the MEK-ERK signaling pathway was identified as the main pathway promoting the upregulation of PD-L1. KRAS mutations promoted PD-L1 expression through the key transcription factor ETV4, which binds to specific sequences in the promoter region of PD-L1 to directly regulate its expression. KRAS mutations promoted PD-L1-mediated immune escape by ETV4. Conclusion: Carcinogenic KRAS mutations in lung adenocarcinoma regulate PD-L1 expression mainly through the MEK-ERK-ETV4 signaling axis. ETV4, as a transcription factor, activates PD-L1 expression and promotes immune escape in KRAS-mutant lung adenocarcinoma.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102525"},"PeriodicalIF":5.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049261","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":"FAP promotes progression of oral leukoplakia via activation of PI3K/AKT pathway by interacting with ITGB1","authors":"Ran Li ,&nbsp;Tiantian Liu ,&nbsp;Yixuan Gu ,&nbsp;Yuantao Gao ,&nbsp;Xiaofeng Jiao ,&nbsp;Yanwei Li ,&nbsp;Songqingmeng Tian ,&nbsp;Kejie Cao","doi":"10.1016/j.tranon.2025.102531","DOIUrl":"10.1016/j.tranon.2025.102531","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to elucidate the molecular mechanisms by which fibroblast activation protein (FAP) contributes to the malignant progression of oral leukoplakia (OLK).</div></div><div><h3>Methods</h3><div>FAP expression was assessed via immunohistochemistry in human OLK and oral squamous cell carcinoma (OSCC) tissues across varying grades of dysplasia (mild, moderate, and severe). DOK and SCC15 cell lines were transfected to modulate FAP expression, followed by functional assays including colony formation, cell viability, transwell migration, and wound healing. Western blot analysis was performed to evaluate the expression of proteins involved in the integrin β1 (ITGB1) /PI3K/AKT pathway. In vivo, FAP-knockdown reagents were administered to OLK lesions in a murine model. Hematoxylin and eosin (HE) staining was used to assess the incidence of dysplasia and OSCC, while immunohistochemistry (IHC) was employed to examine FAP and p-AKT expression.</div></div><div><h3>Results</h3><div>FAP and p-AKT expression levels were positively correlated with the severity of dysplasia in OLK. Mechanistic investigations revealed that FAP enhances malignant behaviors such as proliferation and migration through activation of the ITGB1/PI3K/AKT signaling pathway. Importantly, suppression of FAP significantly reduced the incidence of both oral epithelial dysplasia and OSCC in the mouse model.</div></div><div><h3>Conclusion</h3><div>FAP facilitates the progression of OLK via the ITGB1/PI3K/AKT signaling axis, and its suppression attenuates malignant transformation.</div></div><div><h3>Clinical significance</h3><div>This study highlights the critical involvement of FAP in the malignant transformation of OLK, offering new theoretical foundations for early diagnosis and targeted intervention. The expression level of FAP is positively correlated with the degree of OLK dysplasia, indicating its potential utility as a biomarker for evaluating malignant transformation risk. Moreover, therapeutic approaches targeting FAP or the ITGB1/PI3K/AKT signaling pathway may delay or prevent the progression of OLK to OSCC, presenting promising avenues for the development of precision medicine strategies in clinical practice.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102531"},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049264","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 transcriptome and single-cell RNA sequencing analysis revealed the prognostic significance of GBP4 in pancreatic adenocarcinoma","authors":"Qiyu Chi ,&nbsp;Feihong Liang ,&nbsp;Yaxin Zhang ,&nbsp;Changgan Chen ,&nbsp;Xuling Chen ,&nbsp;Yu Pan ,&nbsp;Shangeng Weng","doi":"10.1016/j.tranon.2025.102532","DOIUrl":"10.1016/j.tranon.2025.102532","url":null,"abstract":"<div><h3>Background</h3><div>The role of GBP4 in cancer has been preliminarily identified, yet its specific function in patients with pancreatic adenocarcinoma (PAAD) remains unclear. The aim of this study is to determine the impact of the GBP4 gene on PAAD.</div></div><div><h3>Methods</h3><div>Transcriptomics and single-cell RNA sequencing (scRNA-seq) data were obtained from public databases. Prognostic genes were screened using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression to construct and validate the model. Pathway enrichment and immune microenvironment analyses explored PAAD mechanisms, while scRNA-seq revealed key cell populations and dynamic gene expression. Functional experiments of GBP4 on tumor cell growth were investigated <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>This study identified 5 prognostic genes related to the GBP4 gene in PAAD, including GBP2, KRT6A, MMP7, BCAT1, and SPRR1A. The risk model showed validity and generalizability, with \"cell cycle\" pathway enrichment in high-risk groups and metabolic pathways in low-risk groups. Immune cell infiltration (e.g., central memory CD8 T cells, activated B cells) differed significantly between risk groups (p &lt; 0.01) and correlated with prognostic genes. Ductal cells were key cells, with prognostic gene expression varying during differentiation. <em>In vitro</em> functional assays confirmed the role of GBP4 in promoting pancreatic cancer cell proliferation, migration, and invasion. Moreover, silencing of GBP4 inhibited tumor growth <em>in vivo</em>, whereas GBP4 overexpression increased the tumor growth.</div></div><div><h3>Conclusion</h3><div>This study identifies GBP4-related prognostic genes and demonstrates the role of GBP4 in pancreatic cancer progression, providing new perspectives for prognostic prediction and therapeutic targeting.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102532"},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049265","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}