Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma

BackgroundCuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated with epigenetic controllers and regulate histone protein modification or DNA methylation during gene tran...

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Main Authors: Guoliang Cui, Jinhui Liu, Can Wang, Renjun Gu, Manli Wang, Zhiguang Sun, Fei Wei
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1007918/full
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author Guoliang Cui
Jinhui Liu
Can Wang
Renjun Gu
Manli Wang
Zhiguang Sun
Fei Wei
author_facet Guoliang Cui
Jinhui Liu
Can Wang
Renjun Gu
Manli Wang
Zhiguang Sun
Fei Wei
author_sort Guoliang Cui
collection DOAJ
description BackgroundCuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated with epigenetic controllers and regulate histone protein modification or DNA methylation during gene transcription. The roles of cuproptosis-related lncRNAs (CRLs) in Colon adenocarcinoma (COAD), however, remain unknown.MethodsCOAD transcriptome data was obtained from the TCGA database. Thirteen genes associated to cuproptosis were identified in published papers. Following that, correlation analysis was used to identify CRLs. The cuproptosis associated prognostic signature was built and evaluated using Lasso regression and COX regression analysis. A prognostic signature comprising six CRLs was established and the expression patterns of these CRLs were analyzed by qRT-PCR. To assess the clinical utility of prognostic signature, we performed tumor microenvironment (TME) analysis, mutation analysis, nomogram generation, and medication sensitivity analysis.ResultsWe identified 49 prognosis-related CRLs in COAD and constructed a prognostic signature consisting of six CRLs. Each patient can be calculated for a risk score and the calculation formula is: Risk score =TNFRSF10A-AS1 * (-0.2449) + AC006449.3 * 1.407 + AC093382.1 *1.812 + AC099850.3 * (-0.0899) + ZEB1-AS1 * 0.4332 + NIFK-AS1 * 0.3956. Six CRLs expressions were investigated by qRT-PCR in three colorectal cancer cell lines. In three cohorts, COAD patients were identified with different risk groups, with the high-risk group having a worse prognosis than the low-risk group. Furthermore, there were differences in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups. We also identified certain drugs that were more sensitive to the high-risk group: Paclitaxel, Vinblastine, Sunitinib and Elescloml.ConclusionsOur findings may be used to further investigate RCD, comprehension of the prognosis and tumor microenvironment infiltration characteristics in COAD.
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spelling doaj.art-03c23c46a0a541748ec7de491082f56e2022-12-22T01:48:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.10079181007918Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinomaGuoliang Cui0Jinhui Liu1Can Wang2Renjun Gu3Manli Wang4Zhiguang Sun5Fei Wei6Department of Gastroenterology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaSchool of Traditional Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaBackgroundCuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated with epigenetic controllers and regulate histone protein modification or DNA methylation during gene transcription. The roles of cuproptosis-related lncRNAs (CRLs) in Colon adenocarcinoma (COAD), however, remain unknown.MethodsCOAD transcriptome data was obtained from the TCGA database. Thirteen genes associated to cuproptosis were identified in published papers. Following that, correlation analysis was used to identify CRLs. The cuproptosis associated prognostic signature was built and evaluated using Lasso regression and COX regression analysis. A prognostic signature comprising six CRLs was established and the expression patterns of these CRLs were analyzed by qRT-PCR. To assess the clinical utility of prognostic signature, we performed tumor microenvironment (TME) analysis, mutation analysis, nomogram generation, and medication sensitivity analysis.ResultsWe identified 49 prognosis-related CRLs in COAD and constructed a prognostic signature consisting of six CRLs. Each patient can be calculated for a risk score and the calculation formula is: Risk score =TNFRSF10A-AS1 * (-0.2449) + AC006449.3 * 1.407 + AC093382.1 *1.812 + AC099850.3 * (-0.0899) + ZEB1-AS1 * 0.4332 + NIFK-AS1 * 0.3956. Six CRLs expressions were investigated by qRT-PCR in three colorectal cancer cell lines. In three cohorts, COAD patients were identified with different risk groups, with the high-risk group having a worse prognosis than the low-risk group. Furthermore, there were differences in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups. We also identified certain drugs that were more sensitive to the high-risk group: Paclitaxel, Vinblastine, Sunitinib and Elescloml.ConclusionsOur findings may be used to further investigate RCD, comprehension of the prognosis and tumor microenvironment infiltration characteristics in COAD.https://www.frontiersin.org/articles/10.3389/fonc.2022.1007918/fullcolon adenocarcinomacuproptosisprognosistumor immune microenvironmentbioinformatics
spellingShingle Guoliang Cui
Jinhui Liu
Can Wang
Renjun Gu
Manli Wang
Zhiguang Sun
Fei Wei
Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
Frontiers in Oncology
colon adenocarcinoma
cuproptosis
prognosis
tumor immune microenvironment
bioinformatics
title Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
title_full Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
title_fullStr Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
title_full_unstemmed Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
title_short Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
title_sort comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis related lncrnas for patients with colon adenocarcinoma
topic colon adenocarcinoma
cuproptosis
prognosis
tumor immune microenvironment
bioinformatics
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1007918/full
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