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Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses

Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the CRC prognosi...

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Autores principales: Tan, Lulu, Xiaohalati, Xiakeerzhati, Liu, Feng, Liu, Jia, Fu, Haoyu, Zhang, Yang, Gao, Jinbo, Tao, Kaixiong, Wang, Guobin, Wang, Lin, Wang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862647/
https://www.ncbi.nlm.nih.gov/pubmed/36675039
http://dx.doi.org/10.3390/ijms24021516
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author Tan, Lulu
Xiaohalati, Xiakeerzhati
Liu, Feng
Liu, Jia
Fu, Haoyu
Zhang, Yang
Gao, Jinbo
Tao, Kaixiong
Wang, Guobin
Wang, Lin
Wang, Zheng
author_facet Tan, Lulu
Xiaohalati, Xiakeerzhati
Liu, Feng
Liu, Jia
Fu, Haoyu
Zhang, Yang
Gao, Jinbo
Tao, Kaixiong
Wang, Guobin
Wang, Lin
Wang, Zheng
author_sort Tan, Lulu
collection PubMed
description Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the CRC prognosis were selected by univariate Cox analyses. Based on these 28 genes, CRC patients were divided into the aging subtype and young subtype by non-negative matrix factorization clustering. Aging subtype and young subtype of CRC were identified with distinct molecular features and clinical prognosis. The aging subtype was characterized by upregulation of senescence-associated secretory phenotype, higher frequencies of TP53 and immune checkpoint molecules, and high sensitivity to protein kinase and angiogenesis inhibitors. Furthermore, 14 genes were selected by LASSO penalized Cox regression analyses for aging-related risk signature construction. The constructed aging risk signature exhibited good prediction and the nomogram showed robust discrimination power over the traditional CRC staging system. In conclusion, this study successfully established aging subtype and young subtype of CRC, which is helpful to identify patients with aging characteristics to evaluate prognosis and treatment outcomes. Introducing aging-based subtypes into clinical concern and patient prognostication provides new opportunities for personalized CRC treatment.
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spelling pubmed-98626472023-01-22 Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses Tan, Lulu Xiaohalati, Xiakeerzhati Liu, Feng Liu, Jia Fu, Haoyu Zhang, Yang Gao, Jinbo Tao, Kaixiong Wang, Guobin Wang, Lin Wang, Zheng Int J Mol Sci Article Colorectal cancer (CRC) is critically related to aging and severely threatens human lives. To better explore the effects of aging on CRC progression and therapy outcome, a reliable aging subtypes identification of CRC is urgently desired. Here, 28 aging-related genes associated with the CRC prognosis were selected by univariate Cox analyses. Based on these 28 genes, CRC patients were divided into the aging subtype and young subtype by non-negative matrix factorization clustering. Aging subtype and young subtype of CRC were identified with distinct molecular features and clinical prognosis. The aging subtype was characterized by upregulation of senescence-associated secretory phenotype, higher frequencies of TP53 and immune checkpoint molecules, and high sensitivity to protein kinase and angiogenesis inhibitors. Furthermore, 14 genes were selected by LASSO penalized Cox regression analyses for aging-related risk signature construction. The constructed aging risk signature exhibited good prediction and the nomogram showed robust discrimination power over the traditional CRC staging system. In conclusion, this study successfully established aging subtype and young subtype of CRC, which is helpful to identify patients with aging characteristics to evaluate prognosis and treatment outcomes. Introducing aging-based subtypes into clinical concern and patient prognostication provides new opportunities for personalized CRC treatment. MDPI 2023-01-12 /pmc/articles/PMC9862647/ /pubmed/36675039 http://dx.doi.org/10.3390/ijms24021516 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tan, Lulu
Xiaohalati, Xiakeerzhati
Liu, Feng
Liu, Jia
Fu, Haoyu
Zhang, Yang
Gao, Jinbo
Tao, Kaixiong
Wang, Guobin
Wang, Lin
Wang, Zheng
Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title_full Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title_fullStr Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title_full_unstemmed Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title_short Identification of Aging and Young Subtypes for Predicting Colorectal Cancer Prognosis and Immunotherapy Responses
title_sort identification of aging and young subtypes for predicting colorectal cancer prognosis and immunotherapy responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862647/
https://www.ncbi.nlm.nih.gov/pubmed/36675039
http://dx.doi.org/10.3390/ijms24021516
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