Translational Oncology最新文献

{"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}

{"title":"Circ-0008536 inhibits doxorubicin resistance in triple-negative breast cancer via the miR-382-5p/GGNBP2 axis","authors":"Xu Liu ,&nbsp;Shaorong Zhao ,&nbsp;Xiaotong Xu ,&nbsp;Xinyu Liu ,&nbsp;Yuchen Zhang ,&nbsp;Siyuan Zhao ,&nbsp;Jingjing Liu ,&nbsp;Jin Zhang","doi":"10.1016/j.tranon.2025.102526","DOIUrl":"10.1016/j.tranon.2025.102526","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) exhibits high intrinsic chemoresistance leading to poor prognosis. We identified circ_-0008536 as a key regulator of doxorubicin (DOX) resistance through integrated transcriptomic analysis, validated by Sanger sequencing and fluorescence in situ hybridization. Circ_-0008536 expression is significantly downregulated in DOX-resistant TNBC patient tissues and cell models, with reduced levels correlating with adverse clinical outcomes. Functionally, including CCK-8 viability assays, EdU proliferation assays, and Annexin V/PI apoptosis assays demonstrated that circ_-0008536 overexpression resensitizes resistant cells to DOX. Mechanistically, circ_-0008536 functions as a competitive endogenous RNA by sequestering miR-382–5p, leading to derepression of the tumor suppressor GGNBP2. This regulatory axis was rigorously evidenced by direct miR-382–5p binding to circ_-0008536 and GGNBP2 3′UTR (dual-luciferase and RIP assays), abrogation of chemosensitivity upon miR-382–5p mimic or GGNBP2 shRNA intervention, and in vivo suppression of tumor growth with enhanced apoptosis in circ_-0008536-overexpressing xenografts. Our findings establish circ_-0008536 as a dual-function prognostic biomarker and therapeutic target for overcoming TNBC chemoresistance through the miR-382–5p/GGNBP2 pathway.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102526"},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049263","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":"Genitourinary system related tumors and coronary atherosclerosis risk: Evidence from a Mendelian randomization study on multi-cohorts","authors":"Shanshan Chen ,&nbsp;Yuanyuan Zhao ,&nbsp;Yang Fan ,&nbsp;Mengchen Zhou","doi":"10.1016/j.tranon.2025.102527","DOIUrl":"10.1016/j.tranon.2025.102527","url":null,"abstract":"<div><h3>Background</h3><div>CVD and cancer are the leading causes of mortality globally. Accumulating evidence suggests that cancer patients have a significantly increased risk of cardiovascular disease. Emerging evidence suggests a bidirectional link between these diseases, possibly mediated by hormonal changes, but further research needs to be performed to explore the specific role of hormone level changes in both diseases.</div></div><div><h3>Methods</h3><div>We conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics from multiple cohorts of prostate cancer, ER+ breast cancer, and coronary atherosclerosis.</div></div><div><h3>Results</h3><div>MR analyses (IVW, MR-Egger, WM) demonstrated a significant causal relationship between both prostate and ER+ breast cancer and increased risk of coronary atherosclerosis.</div></div><div><h3>Conclusion</h3><div>Hormone-related genitourinary tumors may contribute to the development of coronary atherosclerosis. This study is the first to provide causal evidence for such associations using MR.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102527"},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026813","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":"ALAD as a prognostic biomarker regulates metabolism and immune responses in renal cell carcinoma through multi-omics analysis","authors":"Wencheng Gong ,&nbsp;Minghui Ge ,&nbsp;Xiaotong Xi ,&nbsp;Zhongyu Lu ,&nbsp;Xing Zhang ,&nbsp;Dongsheng Chen ,&nbsp;Lijuan Liu","doi":"10.1016/j.tranon.2025.102524","DOIUrl":"10.1016/j.tranon.2025.102524","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC) is a common malignant tumor with metabolic reprogramming and immune evasion features. δ-Aminolevulinic acid dehydratase (ALAD), a key enzyme in heme biosynthesis, has been implicated in cancer progression and treatment outcomes, but its role in RCC remains unclear.</div></div><div><h3>Methods</h3><div>This study integrated multi-omics datasets from TCGA, CPTAC, and GEO to analyze ALAD's expression, prognostic value, and functional implications in RCC.</div></div><div><h3>Results</h3><div>The results showed that ALAD expression is significantly downregulated in RCC tissues at both transcriptomic and proteomic levels, with low expression associated with advanced tumor stages, poor prognosis, and altered metabolic pathways. Functional enrichment and metabolic signature analyses revealed ALAD's association with metabolic processes and immune cell infiltration, particularly impacting CD8+ T cell-mediated immunity. Furthermore, ALAD expression correlated with sensitivity to specific anticancer drugs, suggesting potential therapeutic implications that required functional confirmation.</div></div><div><h3>Conclusion</h3><div>Overall, this study suggestes that ALAD is a promising prognostic biomarker and therapeutic target in RCC, highlighting its role in modulating the tumor immune microenvironment and metabolic landscape. These findings highlight an association between ALAD and RCC progression, though experimental validation is needed to confirm causality.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102524"},"PeriodicalIF":5.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019501","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 and analytical validation of a multiplex diagnostic qPCR-array as a potential application in predicting the response to neoadjuvant chemotherapy in muscle invasive bladder cancer","authors":"Toru Sakatani ,&nbsp;Sunao Tanaka ,&nbsp;Kaoru Murakami ,&nbsp;Francisco Aguilar ,&nbsp;Owen T.M. Chan ,&nbsp;Catherine Bresee ,&nbsp;Daniel J. Luthringer ,&nbsp;Charles J. Rosser ,&nbsp;Wayne Hogrefe ,&nbsp;Hideki Furuya","doi":"10.1016/j.tranon.2025.102528","DOIUrl":"10.1016/j.tranon.2025.102528","url":null,"abstract":"<div><div>Bladder cancer (BC) remains a common malignancy, with muscle-invasive bladder cancer (MIBC) comprising 20 % of cases and a poor 5-year survival rate of ∼50 %. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for locally advanced disease, NAC is limited by toxicity and non-response in many patients. Predictive biomarkers are urgently needed to guide treatment decisions. We developed and analytically validated a multiplex qPCR array to measure mRNA expression of 10 NAC response-associated biomarkers in MIBC. RNA from 8 formalin-fixed paraffin-embedded (FFPE) and 4 fresh-frozen (FF) MIBC specimens was analyzed to assess the effects of tissue type, necrosis, and pre-analytical variables on assay performance. The assay showed high concordance between FF and FFPE samples, with stable performance using FFPE curls stored at ≤4 °C for up to two weeks. It remained robust across RNA input levels (5–100 ng) and required a minimum quality threshold (DV200 &gt;15 %). Necrosis had minimal impact on gene expression, and reproducibility was confirmed across technicians and time points. In conclusion, this qPCR array-based assay offers a reliable platform for evaluating key biomarkers in FFPE tissues and holds promise as a potential clinical tool to predict NAC response in MIBC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102528"},"PeriodicalIF":5.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018678","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":"Novel p53 reactivators that are synergistic with olaparib for the treatment of gynecologic cancers with mutant p53","authors":"Lane E. Smith ,&nbsp;Jamie L. Padilla ,&nbsp;Angelina Licor ,&nbsp;Mara P. Steinkamp ,&nbsp;Irina V. Lagutina ,&nbsp;Yan Guo ,&nbsp;Eric J. Devor ,&nbsp;Vernon S. Pankratz ,&nbsp;Annahita Sallmyr ,&nbsp;Olufunmilola M. Oyebamiji ,&nbsp;Jun-yong Choe ,&nbsp;Geneva L. Williams ,&nbsp;Kimberly K. Leslie","doi":"10.1016/j.tranon.2025.102522","DOIUrl":"10.1016/j.tranon.2025.102522","url":null,"abstract":"<div><div>Ovarian and endometrial cancers frequently harbor a mutation in the tumor suppressor gene <em>TP53</em>, which occurs in over 90 % of ovarian cancers and in the most aggressive endometrial cancers. The normal tumor suppressive functions of p53 are disrupted, resulting in unregulated cell growth and therapeutic resistance to standard treatments including chemotherapy and PARP inhibitors. Hence, a novel therapeutic strategy is urgently needed for p53 mutant gynecologic cancers, and we propose that converting mutant p53 to a wild type conformation and restoring its tumor suppressive functions has the potential to greatly improve treatment. In this study, we investigated the effects of two purported p53 reactivators, HO-3867 and APR-246, on cell proliferation via half-maximal inhibitory concentration (IC50) analyses using CyQUANT DNA measurements, tumor growth <em>in vivo</em> and gene expression by bulk RNA sequencing in gynecologic cancer cell lines that harbor oncogenic mutations in p53. We also tested these compounds in combination with the PARP inhibitor olaparib. We found that HO-3867 was very effective in inhibiting growth, with IC50 values in the low micromolar range. Importantly, HO-3867 was synergistic with olaparib treatment in five cell lines studied <em>in vitro</em> as well as <em>in vivo</em> in a xenograft model of high grade serous ovarian cancer. RNA sequencing data suggest that HO-3867 is acting through both p53-independent and p53-dependent pathways resulting in inhibition of DNA repair pathways including homologous recombination in p53 mutant cancer cells.</div><div><strong>Significance:</strong> The development of resistance to PARP inhibitors is a major problem and a cause of treatment failures in advanced gynecologic cancers, and we show that adding a p53 reactivator such as HO-3867 enhances the efficacy of PARP inhibitors in p53-mutant cancer models.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102522"},"PeriodicalIF":5.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004342","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":"Clinical applications of cell-free DNA-based liquid biopsy analysis","authors":"Shu Yazaki ,&nbsp;Momoko Tokura ,&nbsp;Hisaki Aiba ,&nbsp;Yuki Kojima ,&nbsp;Kouya Shiraishi","doi":"10.1016/j.tranon.2025.102519","DOIUrl":"10.1016/j.tranon.2025.102519","url":null,"abstract":"<div><div>Liquid biopsies, particularly those involving circulating tumor DNA (ctDNA) from patient blood, have emerged as crucial and minimally invasive adjuncts to standard tissue-based testing. ctDNA testing enables the identification of actionable mutations for targeted therapy and can be routinely used when tissue samples are unavailable for genotyping. Compared to tissue-based testing, ctDNA testing has the advantages of capturing spatial or temporal genomic heterogeneity and facilitating repeated assessments. The utility of liquid biopsies extends to multiple clinical applications, including cancer diagnosis, treatment monitoring, and minimal residual disease (MRD) detection. Numerous clinical trials are currently evaluating treatment strategies using ctDNA testing. In particular, the implementation of adjuvant treatment escalation or de-escalation based on MRD detection could dramatically transform future approaches to solid tumor treatment. Various ctDNA assays have been developed, and it is important to understand their strengths and weaknesses for effective clinical applications. Furthermore, ctDNA testing faces several technical challenges, including low sensitivity in detecting copy number alterations and fusions, as well as the possibility of detecting mutations associated with clonal hematopoiesis of indeterminate potential. In this review, we comprehensively discuss the methodologies and recent advancements in cfDNA-based liquid biopsies for cancer patients, covering diagnosis, genomic profiling, and treatment monitoring. Furthermore, we explore clinical trial designs employing ctDNA testing and anticipate forthcoming changes in patient care.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102519"},"PeriodicalIF":5.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003575","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":"NDUFS8 facilitates hepatocellular carcinoma growth by enhancing mitochondrial function and escaping HUWE1-dependent degradation","authors":"Xuxia Zhu ,&nbsp;Ping Lu ,&nbsp;Liang Ji,&nbsp;Qingyu Liang","doi":"10.1016/j.tranon.2025.102521","DOIUrl":"10.1016/j.tranon.2025.102521","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Although mitochondrial metabolism contributes to tumorigenesis, the specific roles of individual mitochondrial components remain unclear.NADH:ubiquinone oxidoreductase core subunit S8 (NDUFS8), a key subunit of mitochondrial complex I, has been implicated in non-hepatic malignancies, but its functional relevance in HCC is unknown.</div></div><div><h3>Methods</h3><div>We assessed NDUFS8 expression in HCC tissues and cell lines using TCGA datasets and patient specimens. Functional analyses—including mitochondrial assays, apoptosis, proliferation, and migration—were performed in NDUFS8-silenced, knockout, and overexpressing HCC cells. In vivo tumor growth was evaluated using xenograft mouse models. Mechanistically, mass spectrometry and immunoprecipitation identified HUWE1 as an E3 ligase responsible for NDUFS8 ubiquitination.</div></div><div><h3>Results</h3><div>NDUFS8 was significantly overexpressed in HCC tissues and cell lines, correlating with poor patient prognosis. NDUFS8 localized to mitochondria and promoted complex I activity and ATP production. Knockdown or knockout of NDUFS8 impaired mitochondrial function, increased ROS, disrupted redox homeostasis, induced apoptosis, and suppressed proliferation and migration of HCC cells. In contrast, NDUFS8 overexpression enhanced oncogenic behaviors. In vivo, NDUFS8 silencing via AAV delivery significantly inhibited xenograft growth and triggered apoptosis. Mechanistically, HUWE1 was identified as a specific E3 ligase that ubiquitinates NDUFS8 at lysine 88, regulating its stability.</div></div><div><h3>Conclusions</h3><div>NDUFS8 is a mitochondrial regulator that promotes HCC progression through metabolic activation and is post-translationally modified by HUWE1. Targeting NDUFS8 or its regulatory axis may represent a promising therapeutic strategy for HCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102521"},"PeriodicalIF":5.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996170","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":"MiR-193b-3p and miR-132-3p as prognostic biomarkers of survival in pleural mesothelioma patients treated with first-line bevacizumab plus pemetrexed-platinum chemotherapy in the IFCT-0701 MAPS phase 3 trial","authors":"Guénaëlle Levallet ,&nbsp;Christian Creveuil ,&nbsp;Alexandre Léger-Vigot ,&nbsp;Solenn Brosseau ,&nbsp;Claire Danel ,&nbsp;Arnaud Scherpereel ,&nbsp;Sylvie Lantuejoul ,&nbsp;Julien Mazières ,&nbsp;Laurent Greillier ,&nbsp;Clarisse Audigier-Valette ,&nbsp;Emmanuel Bergot ,&nbsp;Denis Moro-Sibilot ,&nbsp;Olivier Molinier ,&nbsp;Hervé Léna ,&nbsp;Isabelle Monnet ,&nbsp;Franck Morin ,&nbsp;Valérie Gounant ,&nbsp;Gérard Zalcman","doi":"10.1016/j.tranon.2025.102520","DOIUrl":"10.1016/j.tranon.2025.102520","url":null,"abstract":"<div><div>We investigated whether angiogenesis-related microRNAs (miRNAs) predict survival in patients with pleural mesothelioma (PM) treated with bevacizumab plus pemetrexed-platinum chemotherapy in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456) phase 3 trial phase III trial (NCT00651456). Twelve miRNAs were measured in FFPE samples from 236 of the 448 MAPS trial patients (50.8 %), normalized to RNU48. Overall survival (OS) and progression-free survival (PFS) were analyzed by miRNA expression using univariate and multivariate models adjusted for clinical covariates. Internal validation was performed by bootstrapping. Interaction tests assessed the predictive value of each miRNA with respect to treatment arm. Low miR-193b-3p expression was associated with longer OS in PM patients, as shown in both univariate and multivariate analyses (adjusted HR = 0.87 [0.81–0.93], p &lt; 0.001; bootstrap inclusion fraction [BIF]: 81.3 %), with both treatment arms analyzed together. It also predicted longer PFS (adjusted HR = 0.91 [0.85–0.97], p = 0.0042). Interaction tests revealed that for four miRNAs (miR-155–5p, miR-29c-5p, miR-132–3p, and miR-100–5p), lower expression levels were associated with greater efficacy of the bevacizumab/cisplatin/pemetrexed combination. Notably, the interaction between treatment arms and miR-132–3p expression was statistically significant (p = 0.004). In the IFCT-GFPC-0701 MAPS trial, low miR-193b-3p expression demonstrated significant independent prognostic value, being associated with longer OS and PFS. Additionally, low expression of miR-155–5p, miR-29c-5p, miR-132–3p, and miR-100–5p showed independent predictive value for improved survival in the bevacizumab plus chemotherapy arm. Thus, a simple qRT-PCR assay of these four miRNAs may help identifying PM patients most likely to benefit from bevacizumab.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102520"},"PeriodicalIF":5.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996169","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}