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CPA4作为与膀胱癌免疫细胞浸润相关的不良预后生物标志物的综合分析

Comprehensive Analysis of CPA4 as a Poor Prognostic Biomarker Correlated with Immune Cells Infiltration in Bladder Cancer.

作者信息

Wei Chengcheng, Zhou Yuancheng, Xiong Qi, Xiong Ming, Hou Yaxin, Yang Xiong, Chen Zhaohui

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, Chongqing Medical University, Chongqing 400000, China.

出版信息

Biology (Basel). 2021 Nov 6;10(11):1143. doi: 10.3390/biology10111143.

Abstract

Carboxypeptidase A4 (CPA4) has shown the potential to be a biomarker in the early diagnosis of certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via the TIMER2, STRING, and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA + GETx database. The connection between CPA4 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared with matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that the overexpression of CPA4 is linked with shorter OS, DSF(Disease-specific survival), PFI(Progression-free interval), and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.

摘要

羧肽酶A4(CPA4)已显示出成为某些癌症早期诊断生物标志物的潜力。然而,以前没有研究将CPA4与膀胱癌的治疗或预后意义联系起来。利用来自癌症基因组图谱(TCGA)数据库的数据,我们着手确定CPA4与膀胱癌(BLCA)之间联系的全貌。我们通过TIMER2、STRING和GEPIA2数据库进一步分析了CPA4的相互作用蛋白和浸润免疫细胞。使用TCGA + GETx数据库比较了CPA4在肿瘤组织和正常组织中的表达。使用多变量方法和Kaplan-Meier生存曲线研究了CPA4表达与临床病理特征及总生存期(OS)之间的关系。通过基因集富集分析研究了潜在的功能和途径。此外,我们使用ssGSEA、TIMER2和GEPIA2数据库分析了CPA4表达与浸润免疫细胞及其各自基因标记集之间的关联。与匹配的正常组织相比,发现人类CPA4有大量表达。我们通过Kaplan-Meier和ROC分析证实,CPA4的过表达与较短的OS、疾病特异性生存期(DSF)、无进展生存期(PFI)相关,并增加了诊断潜力。CPA4的表达与T-bet、IL12RB2、CTLA4和LAG3相关,其中T-bet和IL12RB2是Th1标记基因,而CTLA4和LAG3与T细胞耗竭有关,这可能用于指导检查点阻断的应用和T细胞转移疗法的采用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c48/8615209/08c8e2f4d758/biology-10-01143-g001.jpg

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