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通过综合生物信息学分析鉴定和验证胃癌潜在生物标志物

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

作者信息

Sun Chenyu, Chen Yue, Kim Na Hyun, Lowe Scott, Ma Shaodi, Zhou Zhen, Bentley Rachel, Chen Yi-Sheng, Tuason Margarita Whitaker, Gu Wenchao, Bhan Chandur, Tuason John Pocholo Whitaker, Thapa Pratikshya, Cheng Ce, Zhou Qin, Zhu Yanzhe

机构信息

AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, United States.

Department of Clinical Medicine, School of the First Clinical Medicine, Anhui Medical University, Hefei, China.

出版信息

Front Genet. 2022 Jul 15;13:911740. doi: 10.3389/fgene.2022.911740. eCollection 2022.

Abstract

Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

摘要

胃癌(GC)是一种常见且死亡率高的癌症。本研究旨在运用生物信息学方法鉴定其差异表达基因(DEGs)。从四个基因表达综合数据库(GEO)基因表达谱中筛选出DEGs。进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。构建了蛋白质-蛋白质相互作用(PPI)网络。评估了基因表达和预后情况。进行荟萃分析以进一步验证预后。分析了受试者工作特征曲线(ROC)以鉴定诊断标志物,并构建了列线图。开展了药物探索和免疫细胞浸润分析。鉴定出9个上调和3个下调的枢纽基因,它们与胃功能、细胞外活动和结构密切相关。过表达的VIII型胶原蛋白α1链(COL8A1)、X型胶原蛋白α1链(COL10A1)、含胶原蛋白三螺旋重复序列1(CTHRC1)和成纤维细胞活化蛋白(FAP)与预后不良相关。含血小板反应蛋白基序的金属蛋白酶2(ADAMTS2)、COL10A1、XI型胶原蛋白α1链(COL11A1)和CTHRC1的曲线下面积(AUC)>0.9。构建了基于CTHRC1的列线图模型。巨噬细胞、中性粒细胞和树突状细胞的浸润与COL8A1、COL10A1、CTHRC1和FAP呈正相关。荟萃分析证实CTHRC1过表达预后不良。ADAMTS2、COL10A1、COL11A1和CTHRC1在胃癌中具有诊断价值。COL8A1、COL10A1、CTHRC1和FAP与更差的预后相关,具有预后和治疗价值。免疫细胞浸润情况有待进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3f/9337873/9afde3b46b73/fgene-13-911740-g001.jpg

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