Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer

Abstract The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were...

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Autores principales:	Shimin Chen, Wenbo Liu, Yu Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6dd204a0ec3d4f00beb4abdf158bfa84
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spelling	oai:doaj.org-article:6dd204a0ec3d4f00beb4abdf158bfa842021-12-02T18:17:41ZIdentification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer10.1038/s41598-021-86504-82045-2322https://doaj.org/article/6dd204a0ec3d4f00beb4abdf158bfa842021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86504-8https://doaj.org/toc/2045-2322Abstract The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were identified. Univariate Cox analysis was used to screen survival-related genes and multivariate Cox analysis was applied to construct a DNA repair-related gene signature. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. The prognostic model and the expression levels of signature genes were validated using an independent external validation cohort. Two genes (CHAF1A, RMI1) were identified to establish the prognostic signature and patients ware stratified into high- and low-risk groups. Patients in high-risk group presented significant shorter survival time than patients in the low-risk group in both cohorts, which were verified by the ROC curves. Multivariate analysis showed that the prognostic signature was an independent predictor for patients with GC after adjustment for other known clinical parameters. A nomogram incorporating the signature and known clinical factors yielded better performance and net benefits in calibration plot and decision curve analyses. Further, the logistic regression classifier based on the two genes presented an excellent diagnostic power in differentiating early HCC and normal tissues with AUCs higher than 0.9. Moreover, Gene Set Enrichment Analysis revealed that diverse cancer-related pathways significantly clustered in the high-risk and low-risk groups. Immune cell infiltration analysis revealed that CHAF1A and RMI1 were correlated with several types of immune cell subtypes. A prognostic signature using CHAF1A and RMI1 was developed that effectively predicted different OS rates among patients with GC. This risk model provides new clinical evidence for the diagnostic accuracy and survival prediction of GC.Shimin ChenWenbo LiuYu HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shimin Chen Wenbo Liu Yu Huang Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
description	Abstract The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were identified. Univariate Cox analysis was used to screen survival-related genes and multivariate Cox analysis was applied to construct a DNA repair-related gene signature. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. The prognostic model and the expression levels of signature genes were validated using an independent external validation cohort. Two genes (CHAF1A, RMI1) were identified to establish the prognostic signature and patients ware stratified into high- and low-risk groups. Patients in high-risk group presented significant shorter survival time than patients in the low-risk group in both cohorts, which were verified by the ROC curves. Multivariate analysis showed that the prognostic signature was an independent predictor for patients with GC after adjustment for other known clinical parameters. A nomogram incorporating the signature and known clinical factors yielded better performance and net benefits in calibration plot and decision curve analyses. Further, the logistic regression classifier based on the two genes presented an excellent diagnostic power in differentiating early HCC and normal tissues with AUCs higher than 0.9. Moreover, Gene Set Enrichment Analysis revealed that diverse cancer-related pathways significantly clustered in the high-risk and low-risk groups. Immune cell infiltration analysis revealed that CHAF1A and RMI1 were correlated with several types of immune cell subtypes. A prognostic signature using CHAF1A and RMI1 was developed that effectively predicted different OS rates among patients with GC. This risk model provides new clinical evidence for the diagnostic accuracy and survival prediction of GC.
format	article
author	Shimin Chen Wenbo Liu Yu Huang
author_facet	Shimin Chen Wenbo Liu Yu Huang
author_sort	Shimin Chen
title	Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
title_short	Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
title_full	Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
title_fullStr	Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
title_full_unstemmed	Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer
title_sort	identification and external validation of a prognostic signature associated with dna repair genes in gastric cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6dd204a0ec3d4f00beb4abdf158bfa84
work_keys_str_mv	AT shiminchen identificationandexternalvalidationofaprognosticsignatureassociatedwithdnarepairgenesingastriccancer AT wenboliu identificationandexternalvalidationofaprognosticsignatureassociatedwithdnarepairgenesingastriccancer AT yuhuang identificationandexternalvalidationofaprognosticsignatureassociatedwithdnarepairgenesingastriccancer
_version_	1718378281207595008

Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer

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