Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma

Background. Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). Methods. The transcriptome data and clinical variables...

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Autores principales:	Lian Zheng, Yang Yang, Xiaorong Cui
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/1bbee0ebe459430582b70f6582393074
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spelling	oai:doaj.org-article:1bbee0ebe459430582b70f65823930742021-11-22T01:10:48ZEstablishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma2314-614110.1155/2021/4682589https://doaj.org/article/1bbee0ebe459430582b70f65823930742021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4682589https://doaj.org/toc/2314-6141Background. Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). Methods. The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. Results. The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. Conclusion. We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.Lian ZhengYang YangXiaorong CuiHindawi LimitedarticleMedicineRENBioMed Research International, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Lian Zheng Yang Yang Xiaorong Cui Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
description	Background. Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). Methods. The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. Results. The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. Conclusion. We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.
format	article
author	Lian Zheng Yang Yang Xiaorong Cui
author_facet	Lian Zheng Yang Yang Xiaorong Cui
author_sort	Lian Zheng
title	Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
title_short	Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
title_full	Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
title_fullStr	Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
title_full_unstemmed	Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma
title_sort	establishing and validating an aging-related prognostic four-gene signature in colon adenocarcinoma
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/1bbee0ebe459430582b70f6582393074
work_keys_str_mv	AT lianzheng establishingandvalidatinganagingrelatedprognosticfourgenesignatureincolonadenocarcinoma AT yangyang establishingandvalidatinganagingrelatedprognosticfourgenesignatureincolonadenocarcinoma AT xiaorongcui establishingandvalidatinganagingrelatedprognosticfourgenesignatureincolonadenocarcinoma
_version_	1718418325095055360

Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma

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