高表达胰腺腺癌睾丸素预示着与免疫浸润相关的较差预后

IF 1.1 4区 医学 Q4 TOXICOLOGY Molecular & Cellular Toxicology Pub Date : 2024-04-30 DOI:10.1007/s13273-024-00448-4
Rui Chen, Zhengli Zhou, Qihua Dang, Changjing Zuo, Tao Wang
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引用次数: 0

摘要

背景胰腺癌(PAAD)是一种预后极差且缺乏有效生物标志物的恶性肿瘤。方法 本研究利用基因表达谱交互分析(GEPIA)、人类蛋白图谱(HPA)和 Ualcan 数据库测定了 TES 在 PAAD 肿瘤组织和邻近正常胰腺组织中的表达,以及 TES 表达与 PAAD 总生存(OS)的关系。利用肿瘤免疫评估资源(TIMER)数据库评估了TES表达与免疫浸润之间的相关性。利用检索相互作用基因的搜索工具(STRING)数据库构建了TES的蛋白质-蛋白质相互作用(PPI)网络。收集 PAAD 或健康人的组织和血液样本,并使用 qRT-PCR 分析特征基因的表达。TES的表达与浸润B细胞、CD8+ T细胞、巨噬细胞、中性粒细胞和树突状细胞的水平呈正相关。与TES相互作用的前六大枢纽基因HSPB1、VASP、RAB2A、ENAH、ZPR1和THADA均在PAAD中过表达,但只有VASP的表达与PAAD的预后呈负相关。结论 本研究表明,TES 可作为 PAAD 的支持者和预后标志物,它可能通过诱导免疫浸润发挥作用。
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High expression of Testin predicted worse prognosis in pancreatic adenocarcinoma associated with immune infiltration

Background

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with a very poor prognosis and lacks effective biomarkers. Testin (TES) has an altered expression in a variety of cancers, but its expression and role in PAAD remains elusive.

Objectives

To explore the prognosis and biological role of TES in PAAD.

Methods

In this study, the expression of TES in tumor tissues and the adjacent normal pancreatic tissues of PAAD, and the relationship between TES expression and PAAD overall survival (OS), were determined using gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA) and Ualcan database. The correlation between TES expression and immune infiltration was assessed using tumor immunity estimation resource (TIMER) database. Protein–protein interaction (PPI) network of TES was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Tissue and blood samples from PAAD or healthy subjects were collected, and the expression of signature genes was analyzed using qRT–PCR.

Results

Our results showed that TES overexpression occurred in PAAD, and predicted worse prognosis. TES expression was positively correlated with the levels of infiltrating B cells, CD8+ T cells, macrophages, neutrophils and dendritic cells. The top six hub genes HSPB1, VASP, RAB2A, ENAH, ZPR1 and THADA that interact with TES were identified, and they all were overexpression in PAAD, but only VASP expression was negatively correlated with PAAD prognosis. In our samples, compared with the adjacent normal tissues, a higher expression of TES and VASP in PAAD tumor tissues was validated.

Conclusions

The present study suggested that TES could function as a supporter and prognostic marker of PAAD, and it might work via inducing immune infiltration.

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来源期刊
CiteScore
2.50
自引率
17.60%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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