{"title":"Correlation between the decreased expression of NUDT18 and tumor progression in endometrial cancer.","authors":"Yue Hua, Mengdan Miao, Yan Wang, Huaijun Zhou","doi":"10.21037/tcr-2024-2538","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Nudix hydrolase 18 (NUDT18) belongs to the family of nudix hydrolases. This study aimed to clarify the relationship between NUDT18 and endometrial cancer (EC) and whether it is a prognostic factor for EC.</p><p><strong>Methods: </strong>We first examined the function of NUDT18 through The Cancer Genome Atlas public data and Human Protein Atlas databases, and then immunohistochemical staining was conducted to compare the expression of NUDT18 in normal endometrium and EC tissues of different stages. Finally, we performed gene set enrichment analysis (GSEA) to identify the signaling pathways regulated by NUDT18 in EC.</p><p><strong>Results: </strong>We found that NUDT18 expression was considerably elevated in EC tissues relative to physiological endometrium (P<0.001). However, Kaplan-Meier analysis revealed that high NUDT18 expression in EC was associated with a longer overall survival (OS). Immunohistochemistry results showed that NUDT18 expression was upregulated in tissues of early-stage EC compared with normal endometrial tissues and gradually decreased with the increase of stage. NUDT18 expression was significantly associated with Federation of Gynecology and Obstetrics stage, histologic grade, and myometrial invasion (all P values <0.05). GSEA revealed that the biological pathways that were differentially downregulated in the NUDT18-high expression phenotype were cell cycle, the TGF-β signaling pathway, RNA degradation, adherens junction, basal transcription factors, and DNA replication. In addition, NUDT18 DNA copy gain and the downregulation of miR-758-3p exhibited a correlation with the upregulation of NUDT18 in EC, and NUDT18 expression was significantly reduced in tumors with the TP53 mutation. The analysis of immune cell abundance indicated a substantial increase in immune infiltration in EC tissues with high NUDT18 expression.</p><p><strong>Conclusions: </strong>NUDT18 was upregulated in EC relative to normal endometrium, and its expression inversely correlated with tumor stage. Notably, higher NUDT18 expression predicted improved OS, highlighting its clinical significance as a marker of favorable prognosis in EC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4279-4292"},"PeriodicalIF":1.7000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335699/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2024-2538","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/25 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Nudix hydrolase 18 (NUDT18) belongs to the family of nudix hydrolases. This study aimed to clarify the relationship between NUDT18 and endometrial cancer (EC) and whether it is a prognostic factor for EC.
Methods: We first examined the function of NUDT18 through The Cancer Genome Atlas public data and Human Protein Atlas databases, and then immunohistochemical staining was conducted to compare the expression of NUDT18 in normal endometrium and EC tissues of different stages. Finally, we performed gene set enrichment analysis (GSEA) to identify the signaling pathways regulated by NUDT18 in EC.
Results: We found that NUDT18 expression was considerably elevated in EC tissues relative to physiological endometrium (P<0.001). However, Kaplan-Meier analysis revealed that high NUDT18 expression in EC was associated with a longer overall survival (OS). Immunohistochemistry results showed that NUDT18 expression was upregulated in tissues of early-stage EC compared with normal endometrial tissues and gradually decreased with the increase of stage. NUDT18 expression was significantly associated with Federation of Gynecology and Obstetrics stage, histologic grade, and myometrial invasion (all P values <0.05). GSEA revealed that the biological pathways that were differentially downregulated in the NUDT18-high expression phenotype were cell cycle, the TGF-β signaling pathway, RNA degradation, adherens junction, basal transcription factors, and DNA replication. In addition, NUDT18 DNA copy gain and the downregulation of miR-758-3p exhibited a correlation with the upregulation of NUDT18 in EC, and NUDT18 expression was significantly reduced in tumors with the TP53 mutation. The analysis of immune cell abundance indicated a substantial increase in immune infiltration in EC tissues with high NUDT18 expression.
Conclusions: NUDT18 was upregulated in EC relative to normal endometrium, and its expression inversely correlated with tumor stage. Notably, higher NUDT18 expression predicted improved OS, highlighting its clinical significance as a marker of favorable prognosis in EC.
背景：Nudix水解酶18 （NUDT18）属于Nudix水解酶家族。本研究旨在阐明NUDT18与子宫内膜癌（EC）之间的关系及其是否为EC的预后因素。方法：首先通过the Cancer Genome Atlas公开数据和Human Protein Atlas数据库检测NUDT18的功能，然后通过免疫组化染色比较NUDT18在正常子宫内膜和不同分期EC组织中的表达情况。最后，我们进行了基因集富集分析（GSEA），以确定NUDT18在EC中调控的信号通路。结果：我们发现，与生理子宫内膜相比，NUDT18在EC组织中的表达明显升高(p结论：与正常子宫内膜相比，NUDT18在EC组织中的表达上调，且其表达与肿瘤分期呈负相关。值得注意的是，NUDT18的高表达预示着OS的改善，凸显了其作为EC预后良好标志的临床意义。
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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