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一种新型胃腺癌患者预后预测模型的开发与验证

Development and Validation of a Novel Prognosis Prediction Model for Patients With Stomach Adenocarcinoma.

作者信息

Wang Tong, Wen Weiwei, Liu Hongfei, Zhang Jun, Zhang Xiaofeng, Wang Yu

机构信息

School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou, China.

出版信息

Front Med (Lausanne). 2021 Dec 22;8:793401. doi: 10.3389/fmed.2021.793401. eCollection 2021.

Abstract

Stomach adenocarcinoma (STAD) is a significant global health problem. It is urgent to identify reliable predictors and establish a potential prognostic model. RNA-sequencing expression data of patients with STAD were downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Gene expression profiling and survival analysis were performed to investigate differentially expressed genes (DEGs) with significant clinical prognosis value. Overall survival (OS) analysis and univariable and multivariable Cox regression analyses were performed to establish the prognostic model. Protein-protein interaction (PPI) network, functional enrichment analysis, and differential expression investigation were also performed to further explore the potential mechanism of the prognostic genes in STAD. Finally, nomogram establishment was undertaken by performing multivariate Cox regression analysis, and calibration plots were generated to validate the nomogram. A total of 229 overlapping DEGs were identified. Following Kaplan-Meier survival analysis and univariate and multivariate Cox regression analysis, 11 genes significantly associated with prognosis were screened and five of these genes, including COL10A1, MFAP2, CTHRC1, P4HA3, and FAP, were used to establish the risk model. The results showed that patients with high-risk scores have a poor prognosis, compared with those with low-risk scores ( = 0.0025 for the training dataset and = 0.045 for the validation dataset). Subsequently, a nomogram (including TNM stage, age, gender, histologic grade, and risk score) was created. In addition, differential expression and immunohistochemistry stain of the five core genes in STAD and normal tissues were verified. We develop a prognostic-related model based on five core genes, which may serve as an independent risk factor for survival prediction in patients with STAD.

摘要

胃腺癌(STAD)是一个重大的全球健康问题。识别可靠的预测指标并建立潜在的预后模型迫在眉睫。从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库下载了STAD患者的RNA测序表达数据。进行基因表达谱分析和生存分析,以研究具有显著临床预后价值的差异表达基因(DEG)。进行总生存(OS)分析以及单变量和多变量Cox回归分析以建立预后模型。还进行了蛋白质-蛋白质相互作用(PPI)网络、功能富集分析和差异表达研究,以进一步探索STAD中预后基因的潜在机制。最后,通过进行多变量Cox回归分析建立列线图,并生成校准图以验证列线图。共鉴定出总共229个重叠的DEG。经过Kaplan-Meier生存分析以及单变量和多变量Cox回归分析,筛选出11个与预后显著相关的基因,其中包括COL10A1、MFAP2、CTHRC1、P4HA3和FAP这5个基因用于建立风险模型。结果显示,与低风险评分患者相比,高风险评分患者的预后较差(训练数据集P = 0.0025,验证数据集P = 0.045)。随后,创建了一个列线图(包括TNM分期、年龄、性别、组织学分级和风险评分)。此外,还验证了STAD组织和正常组织中5个核心基因的差异表达和免疫组化染色。我们基于5个核心基因开发了一个预后相关模型,该模型可能作为STAD患者生存预测的独立危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa7/8727349/356737ff22dd/fmed-08-793401-g0001.jpg

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