鉴定和验证胃癌患者中 EMT 相关的个体化预后风险评分公式。

Identification and Validation of an Individualized EMT-Related Prognostic Risk Score Formula in Gastric Adenocarcinoma Patients.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Biomed Res Int. 2020 Mar 20;2020:7082408. doi: 10.1155/2020/7082408. eCollection 2020.

DOI:10.1155/2020/7082408

PMID:32309437

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7142392/

Abstract

BACKGROUND

The epithelial-mesenchymal transition (EMT) is a pivotal process for fibrotic disease, embryonic development, and wound healing. Moreover, some evidence has proven that the disorder of EMT also plays an important role in carcinogenesis, especially invasion and metastasis of various tumors (Ritchie et al., 2015). Additionally, gastric adenocarcinoma (GAC) is a common gastrointestinal malignancy which is the fourth most commonly diagnosed tumor. Our study is aimed at identifying the prognostic value of EMT-related genes in gastric adenocarcinoma.

METHODS

Firstly, high-throughput and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. 99 differentially expressed EMT-related genes (ERGs) were obtained in these gastric adenocarcinoma data. Secondly, GO and KEGG enrichment analyses show that EMT may promote gastric carcinogenesis. Next, 10 ERGs associated with prognosis of gastric adenocarcinoma patients are screened out by univariate Cox regression, and 6 pivotal prognostic ERGs (MMP8, MMP11, TFDP3, MYB, F2, and CNTN1) are identified through multivariate Cox regression. These 6 genes are confirmed with significant prognostic value in gastric adenocarcinoma through overall survival (OS) analysis. Finally, a risk score formula is constructed and tested in another gastric adenocarcinoma cohort from GEO.

RESULTS

99 differentially expressed EMT-related genes (ERGs) and their enriched pathways are identified. 10 ERGs are strongly related to the prognosis of GAC patients. A risk score formula of 6 prognosis-related ERGs used to predict the prognosis of gastric adenocarcinoma patients is identified and tested (risk score = 0.448115∗expression value of MMP8 + 0.378892∗expression value of MMP11 - 0.3226∗expression value of MYB + 1.322812∗expression value of TFDP3 + 0.325063∗expression value of F2 + 0.334197∗expression value of CNTN1).

CONCLUSION

This study provides a potential prognostic signature for predicting prognosis of gastric adenocarcinoma patients and molecular insights of EMT in gastric adenocarcinoma, and the formula focusing on the prognosis of gastric adenocarcinoma can be effective.

摘要

背景

上皮-间充质转化（EMT）是纤维化疾病、胚胎发育和伤口愈合的关键过程。此外，有证据表明，EMT 失调在肿瘤发生中也起着重要作用，特别是各种肿瘤的侵袭和转移（Ritchie 等人，2015 年）。此外，胃腺癌（GAC）是一种常见的胃肠道恶性肿瘤，是第四大常见的肿瘤。我们的研究旨在确定 EMT 相关基因在胃腺癌中的预后价值。

方法

首先，从癌症基因组图谱（TCGA）数据库中下载高通量和临床数据。在这些胃腺癌数据中获得了 99 个差异表达的 EMT 相关基因（ERGs）。其次，GO 和 KEGG 富集分析表明 EMT 可能促进胃癌的发生。接下来，通过单因素 Cox 回归筛选出 10 个与胃腺癌患者预后相关的 ERGs，通过多因素 Cox 回归筛选出 6 个关键预后 ERGs（MMP8、MMP11、TFDP3、MYB、F2 和 CNTN1）。通过总生存（OS）分析证实这 6 个基因在胃腺癌中具有显著的预后价值。最后，在 GEO 的另一个胃腺癌队列中构建和测试风险评分公式。

结果

鉴定了 99 个差异表达的 EMT 相关基因（ERGs）及其富集途径。10 个 ERGs 与 GAC 患者的预后密切相关。鉴定并测试了一个基于 6 个预后相关 ERGs 的风险评分公式，用于预测胃腺癌患者的预后（风险评分=0.448115∗MMP8 的表达值+0.378892∗MMP11 的表达值-0.3226∗MYB 的表达值+1.322812∗TFDP3 的表达值+0.325063∗F2 的表达值+0.334197∗CNTN1 的表达值）。