USP5 influences immune infiltration and prognosis in non-small-cell lung cancer

IF 3.7 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-12-01 Epub Date: 2025-10-20 DOI:10.1016/j.prp.2025.156276

Yonghong Xu , Yifei Xie , Jian Zhao , Jiansheng Zhang , Jie Zhao , Yongliang Du , Jianjie Zhu , Yuanyuan Zeng , Jian-an Huang , Zeyi Liu

{"title":"USP5 influences immune infiltration and prognosis in non-small-cell lung cancer","authors":"Yonghong Xu , Yifei Xie , Jian Zhao , Jiansheng Zhang , Jie Zhao , Yongliang Du , Jianjie Zhu , Yuanyuan Zeng , Jian-an Huang , Zeyi Liu","doi":"10.1016/j.prp.2025.156276","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non–small-cell lung cancer (NSCLC) remains to be determined.</div></div><div><h3>Methods</h3><div>USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein–protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan–Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and <em>in vitro</em> functional assays in NSCLC cell lines.</div></div><div><h3>Results</h3><div>USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.</div></div><div><h3>Conclusions</h3><div>USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"276 ","pages":"Article 156276"},"PeriodicalIF":3.7000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathology, research and practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0344033825004698","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/20 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

USP5, a deubiquitinating enzyme, is linked to various cancers. However, its relationship with immune infiltration and its prognostic significance in non–small-cell lung cancer (NSCLC) remains to be determined.

Methods

USP5 expression patterns in NSCLC were analyzed using data sourced from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Functional enrichment analyses were performed to predict the role of USP5 in NSCLC development, and Hub genes were identified through a protein–protein interaction (PPI) network. Immune cell infiltration was assessed via single-sample gene set enrichment analysis, while the prognostic significance of USP5 was evaluated using the Kaplan–Meier method and Cox regression analysis. To facilitate survival rate predictions at different time points, a prognostic model was developed. Previous findings were validated using real-time PCR and in vitro functional assays in NSCLC cell lines.

Results

USP5 expression was found to be markedly elevated in NSCLC tissues when compared to normal tissues. Functional enrichment analysis revealed the involvement of USP5 in regulating key pathways linked to lung adenocarcinoma development. PPI network analysis revealed several potential interactions contributing to NSCLC progression. A correlation was observed between higher USP5 levels and the reduced presence of immune cells (e.g., macrophages, CD8 +T cells, NK cells, and iDCs) within the tumor microenvironment. ROC curves confirmed the prognostic value of USP5 for NSCLC. Functional studies in NSCLC cell lines confirmed the molecular effects of USP5 on NSCLC development.

Conclusions

USP5 appears to be a reliable marker for diagnosing NSCLC and predicting its prognosis. Further investigation into the role of USP5 in immune responses may aid in the development of immunotherapies for NSCLC.

查看原文本刊更多论文

USP5影响非小细胞肺癌的免疫浸润和预后

usp5是一种去泛素化酶，与多种癌症有关。然而，其与免疫浸润的关系及其在非小细胞肺癌（NSCLC）中的预后意义尚不明确。方法利用基因表达图谱（Gene expression Omnibus）和癌症基因组图谱（Cancer Genome Atlas）数据库的数据，分析NSCLC中sus5的表达模式。通过功能富集分析预测USP5在NSCLC发展中的作用，并通过蛋白-蛋白相互作用（PPI）网络鉴定Hub基因。通过单样本基因集富集分析评估免疫细胞浸润，采用Kaplan-Meier法和Cox回归分析评估USP5对预后的意义。为了便于预测不同时间点的生存率，我们建立了一个预后模型。之前的发现通过实时PCR和非小细胞肺癌细胞系的体外功能测定得到了验证。结果与正常组织相比，非小细胞肺癌组织中sus5的表达明显升高。功能富集分析揭示了USP5参与调节与肺腺癌发展相关的关键通路。PPI网络分析揭示了几种促进NSCLC进展的潜在相互作用。观察到USP5水平升高与肿瘤微环境中免疫细胞（如巨噬细胞、CD8 +T细胞、NK细胞和idc）的减少之间存在相关性。ROC曲线证实了USP5对NSCLC的预后价值。NSCLC细胞系的功能研究证实了USP5在NSCLC发展中的分子作用。结论sus5是诊断非小细胞肺癌和预测其预后的可靠标志物。进一步研究USP5在免疫应答中的作用可能有助于开发针对非小细胞肺癌的免疫疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.