Translational Oncology最新文献

{"title":"Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC","authors":"Zehui Yao ,&nbsp;Huihui Zhang ,&nbsp;Kewei Huang ,&nbsp;Guizhong Huang ,&nbsp;Pu Xi ,&nbsp;Lingmin Jiang ,&nbsp;Dailei Qin ,&nbsp;Fan Chen ,&nbsp;Shengping Li ,&nbsp;Ran Wei","doi":"10.1016/j.tranon.2024.102206","DOIUrl":"10.1016/j.tranon.2024.102206","url":null,"abstract":"<div><div>While poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have achieved specific clinical benefits in a subset of pancreatic ductal adenocarcinoma (PDAC) patients, the potential role of the PARPi niraparib in PDAC necessitates further exploration. In this study, we demonstrated that Niraparib exhibited a pronounced inhibitory effect on autophagy in PDAC both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, this inhibition was primarily attributed to niraparib's ability to disrupt the fusion process between autophagosomes and lysosomes, while potentially exerting a relatively minor impact on the initial stage of autophagy. The blockade effect observed may be mediated via modulation of the ERK signaling pathway, and this effect can be mitigated by the application of an ERK inhibitor (FR180204). Notably, the combined treatment regimen of niraparib and gemcitabine failed to elicit the anticipated synergistic effects in wild-type PANC-1 cells, instead exhibiting pronounced antagonistic interactions. However, in gemcitabine-resistant PANC-1 cells, the combination of niraparib and gemcitabine exhibited modest additive effects. Furthermore, niraparib demonstrated a heightened cytotoxic potency against gemcitabine-resistant PANC-1 cells compared to wild-type PANC-1 cells, both <em>in vitro</em> and <em>in vivo</em>. Our research established that niraparib inhibits late-stage autophagy in PDAC, potentially representing a valuable salvage therapy for gemcitabine-resistant PDAC. Further clinical studies are justified.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102206"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting STK26 and ATG4B: miR-22-3p as a modulator of autophagy and tumor progression in HCC","authors":"Kai Li ,&nbsp;Yaping Bai ,&nbsp;Jingtong Wang ,&nbsp;Li Ren ,&nbsp;Anqi Mo ,&nbsp;Rong Liu ,&nbsp;Yun Wang ,&nbsp;Fengcang Zhou ,&nbsp;Wenjun Pei ,&nbsp;Xiuhua Shi","doi":"10.1016/j.tranon.2024.102214","DOIUrl":"10.1016/j.tranon.2024.102214","url":null,"abstract":"<div><div>Drug-induced protective autophagy significantly affects the efficacy of anticancer therapies. Enhancing tumor cell sensitivity to treatment by inhibiting autophagy is essential for effective cancer therapy. Our study, analyzing data from The Cancer Genome Atlas (TCGA) public database, HCC cell lines, and liver cancer tissue samples, found that miR-22-3p is expressed at low levels in HCC and is significantly associated with clinicopathological features and patient prognosis. Functional assays and xenograft models demonstrated that miR-22-3p suppresses HCC progression. Moreover, Western blot analysis and the LC3B double reporter (mRFP1-EGFP-LC3B) confirmed that miR-22-3p inhibits autophagy in HCC cells. Further investigation identified Sterile 20-like kinase 26 (STK26) and Autophagy Related 4B Cysteine Peptidase (ATG4B) as targets of miR-22-3p. STK26, which is overexpressed in HCC, promotes malignant characteristics such as proliferation, migration, and invasion. Additionally, STK26 facilitates autophagy in HCC by phosphorylating ATG4B at serine 383. miR-22-3p inhibits autophagy by targeting STK26 and ATG4B, thus preventing the phosphorylation of ATG4B at serine 383. Sorafenib treatment increases the levels and phosphorylation of STK26 and ATG4B, inducing protective autophagy. The combination of miR-22-3p with sorafenib demonstrated enhanced antitumor effects both in vitro and in vivo. In conclusion, our findings suggest that miR-22-3p inhibits HCC progression by regulating the expression of STK26 and ATG4B, potentially through autophagy inhibition, thereby increasing sensitivity to sorafenib treatment. This offers a new therapeutic approach for effective HCC</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102214"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a radiomic prediction model for TACC3 expression and prognosis in non-small cell lung cancer using contrast-enhanced CT imaging","authors":"Weichao Bai ,&nbsp;Xinhan Zhao ,&nbsp;Qian Ning","doi":"10.1016/j.tranon.2024.102211","DOIUrl":"10.1016/j.tranon.2024.102211","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Non-small cell lung cancer (NSCLC) prognosis remains poor despite treatment advances, and classical prognostic indicators often fall short in precision medicine. Transforming acidic coiled-coil protein-3 (<em>TACC3</em>) has been identified as a critical factor in tumor progression and immune infiltration across cancers, including NSCLC. Predicting <em>TACC3</em> expression through radiomic features may provide valuable insights into tumor biology and aid clinical decision-making. However, its predictive value in NSCLC remains unexplored. Therefore, we aimed to construct and validate a radiomic model to predict <em>TACC3</em> levels and prognosis in patients with NSCLC.</div></div><div><h3>Materials and methods</h3><div>Genomic data and contrast-enhanced computed tomography (CT) images were sourced from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database, and The Cancer Imaging Archive (TCIA). A total of 320 cases of lung adenocarcinoma from TCGA and 122 cases of NSCLC from GEO were used for prognostic analysis. Sixty-three cases from TCIA and GEO were included for radiomics feature extraction and model development. The radiomics model was constructed using logistic regression (LR) and support vector machine (SVM) algorithms. We predicted <em>TACC3</em> expression and evaluated its correlation with NSCLC prognosis using contrast-enhanced CT-based radiomics.</div></div><div><h3>Results</h3><div><em>TACC3</em> expression significantly influenced NSCLC prognosis. High TACC3 levels were associated with reduced overall survival, potentially mediated by immune microenvironment and tumor progression regulation. LR and SVM algorithms achieved AUC of 0.719 and 0.724, respectively, which remained at 0.701 and 0.717 after five-fold cross-validation.</div></div><div><h3>Conclusion</h3><div>Contrast-enhanced CT-based radiomics can non-invasively predict <em>TACC3</em> expression and provide valuable prognostic information, contributing to personalized treatment strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102211"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein B/Apolipoprotein A1 ratio is an independent prognostic factor in pancreatic cancer","authors":"Chenxi Li ,&nbsp;Xuhui Yang ,&nbsp;Yan Zhong ,&nbsp;Wenying Wang ,&nbsp;Xin Jin ,&nbsp;Lihua Bian ,&nbsp;Xiaona Wang","doi":"10.1016/j.tranon.2024.102208","DOIUrl":"10.1016/j.tranon.2024.102208","url":null,"abstract":"<div><h3>Objective</h3><div>The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer.</div></div><div><h3>Methods</h3><div>A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model.</div></div><div><h3>Results</h3><div>Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA1), high ApoB/ApoA1 level indicated a shorter OS (HR:2.028, 95% CI: 1.174–2.504, <em>P</em> = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076–3.009, <em>P</em> = 0.025). Other serum lipid molecules were not associated with PFS and OS.</div></div><div><h3>Conclusion</h3><div>ApoB/ApoA1 might be an independent prognostic factor of pancreatic cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102208"},"PeriodicalIF":5.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BET inhibitor and CDK4/6 inhibitor synergistically inhibit breast cancer by suppressing BRD4 stability and DNA damage repair","authors":"Shuaishuai Chi ,&nbsp;Fan Wei ,&nbsp;Yangsha Li ,&nbsp;Lei Yu ,&nbsp;Chuyao Ma ,&nbsp;Yanfen Fang ,&nbsp;Biyu Yang ,&nbsp;Yi Chen ,&nbsp;Jian Ding","doi":"10.1016/j.tranon.2024.102212","DOIUrl":"10.1016/j.tranon.2024.102212","url":null,"abstract":"<div><div>CDK4/6 inhibitors have shown clinical benefits in hormone receptor positive breast cancer. However, monotonous indications and unclear resistance mechanisms greatly limit the clinical application of these inhibitors. We attempt to improve the therapeutic effect of CDK4/6 inhibitors against breast cancer by combination with BET inhibitors. Although this combination therapy has begun to be studied in recent clinical trials, the mechanism of action is not clear. We provide the evidence that CDK4/6 inhibitor LY2835219 plus BRD4 inhibitor OTX-015 synergistically inhibits both ER positive and triple-negative breast cancer cells growth <em>in vitro</em> and <em>in vivo</em>. Mechanistically, LY2835219 accelerates the degradation of BRD4 through the proteasome pathway <em>via</em> inhibition of CDK4 activity. This instability of BRD4 protein in turn enhances the anti-tumor effect of CDK4/6 inhibitor by suppressing transcription of DNA damage repair gene <em>RAD51</em>, and synergistically promotes γ-H2AX accumulation and DNA double-strand breaks. Overall, we demonstrated the potential combined therapeutic value of CDK4/6 and BRD4 inhibitors and elucidated the mechanisms, which may provide a new rational approach for breast cancer patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102212"},"PeriodicalIF":5.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma","authors":"Hu Wang ,&nbsp;Yilong Gao ,&nbsp;Fengran Guo ,&nbsp;Pengfei Zhou ,&nbsp;Ziyang Ma ,&nbsp;Kui Chi ,&nbsp;Jiaqing Ye ,&nbsp;Hao Sun ,&nbsp;Xingyu He ,&nbsp;Bei Shi ,&nbsp;Yaxuan Wang ,&nbsp;Zhenwei Han","doi":"10.1016/j.tranon.2024.102213","DOIUrl":"10.1016/j.tranon.2024.102213","url":null,"abstract":"<div><h3>Background</h3><div>Our previous studies have shown that estrogen receptor beta (<em>ERβ</em>) can promote the progression of clear cell renal cell carcinoma (ccRCC) by downregulating the expression of circATP2B1 and miR-204–3p. Here, we found that ERβ might promote the epithelial-mesenchymal transition(EMT) of ccRCC by modulating the circATP2B1/miR-204–3p/TWIST1(Twist family basic helix-loop-helix transcription factor 1) signaling pathway.</div></div><div><h3>Methods</h3><div>We utilized bioinformatics analysis to determine the clinical significance of TWIST1 in ccRCC. The expression of TWIST1 in ccRCC tissues and cells was examined using immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting assay. Chromatin Immunoprecipitation assay were conducted to validate the relationship between <em>ERβ</em> and TWIST1. Luciferase reporter gene assays were employed to validate the binding targets of TWIST1 and miR-204–3p. The role of <em>TWIST1</em> in ccRCC was studied through <em>in vitro</em> and <em>in vivo</em> experiments. Transwell assays and wound healing assays were used to assess the impact of TWIST1 on the invasive and migratory abilities of ccRCC cells.</div></div><div><h3>Results</h3><div>Mechanism analysis revealed that miR-204–3p can inhibit <em>TWIST1</em> by targeting its 3′ untranslated region. Additionally, TWIST1 can promote <em>ERβ</em> transcription by directly binding to transcription factor binding site in the ERβ promoter region, forming a positive feedback loop. These <em>in vitro</em> data were further validated in an <em>in vivo</em> mouse model. Importantly, analysis of data from the TCGA-KIRC database further confirmed the above <em>in vitro</em>/<em>in vivo</em> findings.</div></div><div><h3>Conclusions</h3><div>Together, our results suggest that ERβ/circATP2B1/miR-204–3p/TWIST1 can promote EMT by forming a positive feedback loop, thus promoting the progression of ccRCC. Targeting this newly identified signaling pathway may more effectively control the progression of ccRCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102213"},"PeriodicalIF":5.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of serum MUC17 as a non‐invasive early warning biomarker for screening of gastric intraepithelial neoplasia","authors":"Bingxue Yang ,&nbsp;Xiaoli Xie ,&nbsp;Xiaoxu Jin,&nbsp;Xiuhong Huang,&nbsp;Yujian He,&nbsp;Kaige Yin,&nbsp;Chenguang Ji,&nbsp;Li Liu,&nbsp;Zhijie Feng","doi":"10.1016/j.tranon.2024.102207","DOIUrl":"10.1016/j.tranon.2024.102207","url":null,"abstract":"<div><h3>Background</h3><div>The early diagnosis and treatment of Gastric Intraepithelial Neoplasia (GIN) are pivotal for improving the survival rates of patients with gastric cancer (GC). Regrettably, reliable noninvasive biomarkers for GIN screening are currently lacking.</div></div><div><h3>Methods</h3><div>mRNA data from the GEO database, pan-cancer data from the TCGA database, and a gene list of exocrine proteins were subjected to integrated analysis to identify a noninvasive biomarker for GIN. The scRNA-seq data analysis, IHC and Elisa were employed to validate the expression of the biomarker in the serum and tissues of clinical patients across different pathological stages.</div></div><div><h3>Results</h3><div>MUC17 has been identified as a non-invasive diagnostic marker for GIN. It is upregulated in GIN prior to the onset of gastric carcinogenesis and downregulated in other tumors, with high GC specificity. The area under the curve values of serum MUC17 for differentiating chronic gastritis (CG) from low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and early gastric cancer (EGC) were 0.8788, 0.8544, and 0.9513, respectively. Additionally, low plasma MUC17 levels were found to be significantly lower in gastric ulcer (GU), gastric neuroendocrine tumor (GNET), and gastrointestinal stromal tumor (GIST) compared to GIN. The AUC for differentiating between GIN and GU, GNET, or GIST was 0.7803, 0.9244 and 0.9796, respectively.</div></div><div><h3>Conclusions</h3><div>These findings suggest that plasma MUC17 levels hold substantial promise as a screening biomarker for individuals with GIN and EGC, effectively identifying high-risk groups that necessitate further gastroscopy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102207"},"PeriodicalIF":5.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate cancer risk biomarkers from large cohort and prospective metabolomics studies: A systematic review","authors":"Yamilé López-Hernández ,&nbsp;Cristina Andres-Lacueva ,&nbsp;David S. Wishart ,&nbsp;Claudia Torres-Calzada ,&nbsp;Miriam Martínez-Huélamo ,&nbsp;Enrique Almanza-Aguilera ,&nbsp;Raul Zamora-Ros","doi":"10.1016/j.tranon.2024.102196","DOIUrl":"10.1016/j.tranon.2024.102196","url":null,"abstract":"<div><div>Prostate cancer (PCa) is one of the leading causes of cancer-related deaths among men. The heterogeneous nature of this disease presents challenges in its diagnosis, prognosis, and treatment. Numerous potential predictive, diagnostic, prognostic, and risk assessment biomarkers have been proposed through various population studies. However, to date, no metabolite biomarker has been approved or validated for the diagnosis, prognosis, or risk assessment of PCa. Recognizing that systematic reviews of case reports or heterogenous studies cannot reliably establish causality, this review analyzed 29 large prospective metabolomics studies that utilized harmonized criteria for patient selection, consistent methodologies for blood sample collection and storage, data analysis, and that are available in public repositories. By focusing on these large prospective studies, we identified 42 metabolites that were consistently replicated by different authors and across cohort studies. These metabolites have the potential to serve as PCa risk-assessment or predictive biomarkers. A discussion on their associations with dietary sources or dietary patterns is also provided. Further detailed exploration of the relationship with diet, supplement intake, nutrition patterns, contaminants, lifestyle factors, and pre-existing comorbidities that may predispose individuals to PCa is warranted for future research and validation.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102196"},"PeriodicalIF":5.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review","authors":"Yaochun Wang ,&nbsp;Jingzhuo Song ,&nbsp;Shuxing Zheng ,&nbsp;Shuhong Wang","doi":"10.1016/j.tranon.2024.102193","DOIUrl":"10.1016/j.tranon.2024.102193","url":null,"abstract":"<div><div>Von Hippel-Lindau Syndrome (VHL) is a rare genetic disorder characterized by tumors in multiple organs, including the kidneys, pancreas, and central nervous system. This comprehensive review discusses the genetic basis and clinical manifestations of VHL, as well as recent advancements in understanding the molecular mechanisms that lead to tumor formation. The authors highlight the role of hypoxia-inducible factors and the ubiquitin-proteasome system in VHL-associated cancer development .The review also discusses the potential clinical implications of these findings, such as the development of targeted therapies for VHL-associated cancers. However, the authors note the challenges associated with developing effective treatments for this complex disease, including limited patient availability for clinical trials due to its rarity .Overall, this review provides valuable insights into our current understanding of VHL and offers important avenues for future research aimed at improving the diagnosis, treatment, and management of VHL patients. By illuminating the molecular underpinnings of VHL-associated cancers, this work may ultimately help to develop more effective treatments and improve outcomes for patients with this challenging disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102193"},"PeriodicalIF":5.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients","authors":"Ying Huang ,&nbsp;Jing Jin ,&nbsp;Ningxin Ren ,&nbsp;Hongxia Chen ,&nbsp;Yan Qiao ,&nbsp;Shuangmei Zou ,&nbsp;Xin Wang ,&nbsp;Linlin Zheng ,&nbsp;Ye-Xiong Li ,&nbsp;Wen Tan ,&nbsp;Dongxin Lin","doi":"10.1016/j.tranon.2024.102203","DOIUrl":"10.1016/j.tranon.2024.102203","url":null,"abstract":"<div><div>The identification a signature comprising a group of genes as markers of cancer response to chemoradiotherapy would be more appropriate and effective for predicting chemoradiotherapy efficacy. This study investigated the differentially expressed genes (DEGs) related to chemoradiotherapy resistance and established a multigene expression model for predicting the sensitivity of rectal cancer to chemoradiotherapy in rectal cancer patients, elucidated the mechanism of resistance to synchronized chemoradiotherapy. The genome-wide expression profiling microarray were performed in the tissues of 81 rectal cancer patients before neoadjuvant therapy to analyze and discover DEGs related to chemoradiotherapy resistance, and the results were verified in 45 rectal cancer patients, and finally a 20-gene signature was proposed to be a predictor of chemoradiotherapy response. Molecular biology experiments revealed that zinc finger protein 37A (ZNF37A) downregulation leads to therapeutic resistance. This study identified a 20-gene signature with group of genes can help predict the response to chemoradiotherapy of rectal cancer patients. ZNF37A demonstrated a statistically significant correlation with sensitivity to chemoradiotherapy and survival in patients with LARC who underwent chemoradiotherapy. The findings revealed that ZNF37A bound to the tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) promoter region, thereby suppressing its transcriptional activity. Reduced expression of ZNF37A induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer (CRC) cells. TNFRSF6B Knockdown restored the sensitivity of CRC to chemoradiotherapy. ZNF37A is an effective modulator of chemoradiotherapy response in rectal cancer. These findings elucidate the molecular mechanism underlying chemoradiotherapy resistance and provide potential applications for individualized clinical therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102203"},"PeriodicalIF":5.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}