{"title":"<i>NAT2</i>: A Novel Target in Intrahepatic Cholangiocarcinoma and its Role in Modulating Tumor Behavior.","authors":"Xiyun Chen, Guang Yang, Cheng Lou, Yulong Dong, Zhengang Yuan","doi":"10.1177/11795549251360481","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.</p><p><strong>Methods: </strong>Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.</p><p><strong>Results: </strong>The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (<i>P</i> < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (<i>P</i> < .01). The NAT2 knockdown reduced RBE cell proliferation (<i>P</i> < .001) and increased late apoptosis (<i>P</i> < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (<i>P</i> < .05), supporting NAT2's role in regulating ICC cell apoptosis.</p><p><strong>Conclusion: </strong>NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251360481"},"PeriodicalIF":1.9000,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358714/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Medicine Insights-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/11795549251360481","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.
Methods: Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.
Results: The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (P < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (P < .01). The NAT2 knockdown reduced RBE cell proliferation (P < .001) and increased late apoptosis (P < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (P < .05), supporting NAT2's role in regulating ICC cell apoptosis.
Conclusion: NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.
背景：肝内胆管癌（ICC）是一种原发性肝癌，通常在晚期诊断，限制了治疗选择并降低了生存率。靶向治疗是一种改善预后的有希望的策略。本研究旨在发现影响ICC发展的新型分子生物标志物，并探讨其在肿瘤进展中的作用。方法：采用加权基因共表达网络分析（WGCNA）对来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据进行分析，找出与肿瘤转移和复发相关的基因。生存分析和基因集富集分析（GSEA）评估基因表达与生存的关系，以及相关的信号通路。进行细胞实验，包括小干扰RNA （siRNA）敲除、细胞活力测定、Transwell迁移测定和流式细胞术。结果：Kaplan-Meier分析显示，n-乙酰转移酶2 （NAT2）高表达的ICC患者的生存时间明显短于低表达的ICC患者（P P P P P P P）。结论：NAT2是一种新的治疗靶点，具有显著改善ICC患者预后的潜力。
期刊介绍：
Clinical Medicine Insights: Oncology is an international, peer-reviewed, open access journal that focuses on all aspects of cancer research and treatment, in addition to related genetic, pathophysiological and epidemiological topics. Of particular but not exclusive importance are molecular biology, clinical interventions, controlled trials, therapeutics, pharmacology and drug delivery, and techniques of cancer surgery. The journal welcomes unsolicited article proposals.
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