Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer

Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-...

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Autores principales:	Xu-tao Lin, Qiu-ning Wu, Si Qin, De-jun Fan, Min-yi Lv, Xi Chen, Jia-wei Cai, Jing-rong Weng, Yi-feng Zou, Yu-ming Rong, Feng Gao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer prognosis early stage disease-free survival autophagy-related gene Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2be0498ee9e34a008809051b7a3d9a29
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spelling	oai:doaj.org-article:2be0498ee9e34a008809051b7a3d9a292021-12-01T03:28:33ZIdentification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer1664-802110.3389/fgene.2021.755789https://doaj.org/article/2be0498ee9e34a008809051b7a3d9a292021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.755789/fullhttps://doaj.org/toc/1664-8021Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified.Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; p = 2.06 × 10–4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; p = 1.5 × 10–2) and meta-validation cohorts (HR, 2.5[1.03–6.06]; p = 3.63 × 10–2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed.Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.Xu-tao LinXu-tao LinQiu-ning WuQiu-ning WuSi QinSi QinDe-jun FanDe-jun FanMin-yi LvMin-yi LvXi ChenXi ChenJia-wei CaiJia-wei CaiJing-rong WengJing-rong WengYi-feng ZouYi-feng ZouYu-ming RongFeng GaoFeng GaoFrontiers Media S.A.articlecolorectal cancerprognosisearly stagedisease-free survivalautophagy-related geneGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer prognosis early stage disease-free survival autophagy-related gene Genetics QH426-470
spellingShingle	colorectal cancer prognosis early stage disease-free survival autophagy-related gene Genetics QH426-470 Xu-tao Lin Xu-tao Lin Qiu-ning Wu Qiu-ning Wu Si Qin Si Qin De-jun Fan De-jun Fan Min-yi Lv Min-yi Lv Xi Chen Xi Chen Jia-wei Cai Jia-wei Cai Jing-rong Weng Jing-rong Weng Yi-feng Zou Yi-feng Zou Yu-ming Rong Feng Gao Feng Gao Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
description	Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified.Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; p = 2.06 × 10–4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; p = 1.5 × 10–2) and meta-validation cohorts (HR, 2.5[1.03–6.06]; p = 3.63 × 10–2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed.Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.
format	article
author	Xu-tao Lin Xu-tao Lin Qiu-ning Wu Qiu-ning Wu Si Qin Si Qin De-jun Fan De-jun Fan Min-yi Lv Min-yi Lv Xi Chen Xi Chen Jia-wei Cai Jia-wei Cai Jing-rong Weng Jing-rong Weng Yi-feng Zou Yi-feng Zou Yu-ming Rong Feng Gao Feng Gao
author_facet	Xu-tao Lin Xu-tao Lin Qiu-ning Wu Qiu-ning Wu Si Qin Si Qin De-jun Fan De-jun Fan Min-yi Lv Min-yi Lv Xi Chen Xi Chen Jia-wei Cai Jia-wei Cai Jing-rong Weng Jing-rong Weng Yi-feng Zou Yi-feng Zou Yu-ming Rong Feng Gao Feng Gao
author_sort	Xu-tao Lin
title	Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
title_short	Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
title_full	Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
title_fullStr	Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
title_full_unstemmed	Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer
title_sort	identification of an autophagy-related gene signature for the prediction of prognosis in early-stage colorectal cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2be0498ee9e34a008809051b7a3d9a29
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Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer

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