Cargando…
A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma
Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meanin...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256842/ https://www.ncbi.nlm.nih.gov/pubmed/34235071 http://dx.doi.org/10.3389/fonc.2021.612952 |
_version_ | 1783718178706161664 |
---|---|
author | Ye, Zaisheng Zheng, Miao Zeng, Yi Wei, Shenghong Huang, He Wang, Yi Liu, Qinying Lin, Zhitao Chen, Shu Zheng, Qiuhong Chen, Luchuan |
author_facet | Ye, Zaisheng Zheng, Miao Zeng, Yi Wei, Shenghong Huang, He Wang, Yi Liu, Qinying Lin, Zhitao Chen, Shu Zheng, Qiuhong Chen, Luchuan |
author_sort | Ye, Zaisheng |
collection | PubMed |
description | Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meaningful. An integrative analysis was performed with 407 samples from The Cancer Genome Atlas (TCGA) and 433 samples from Gene Expression Omnibus (GEO) to develop a metabolic prognostic signature associated with clinical and immune features in STAD using Cox regression analysis and least absolute shrinkage and selection operator (LASSO). The different proportions of immune cells and differentially expressed immune-related genes (DEIRGs) between high- and low-risk score groups based on the metabolic prognostic signature were evaluated to describe the association of cancer metabolism and immune response in STAD. A total of 883 metabolism-related genes in both TCGA and GEO databases were analyzed to obtain 184 differentially expressed metabolism-related genes (DEMRGs) between tumor and normal tissues. A 13-gene metabolic signature (GSTA2, POLD3, GLA, GGT5, DCK, CKMT2, ASAH1, OPLAH, ME1, ACYP1, NNMT, POLR1A, and RDH12) was constructed for prognostic prediction of STAD. Sixteen survival-related DEMRGs were significantly related to the overall survival of STAD and the immune landscape in the tumor microenvironment. Univariate and multiple Cox regression analyses and the nomogram proved that a metabolism-based prognostic risk score (MPRS) could be an independent risk factor. More importantly, the results were mutually verified using TCGA and GEO data. This study provided a metabolism-related gene signature for prognostic prediction of STAD and explored the association between metabolism and the immune microenvironment for future research, thereby furthering the understanding of the crosstalk between different molecular mechanisms in human STAD. Some prognosis-related metabolic pathways have been revealed, and the survival of STAD patients could be predicted by a risk model based on these pathways, which could serve as prognostic markers in clinical practice. |
format | Online Article Text |
id | pubmed-8256842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82568422021-07-06 A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma Ye, Zaisheng Zheng, Miao Zeng, Yi Wei, Shenghong Huang, He Wang, Yi Liu, Qinying Lin, Zhitao Chen, Shu Zheng, Qiuhong Chen, Luchuan Front Oncol Oncology Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meaningful. An integrative analysis was performed with 407 samples from The Cancer Genome Atlas (TCGA) and 433 samples from Gene Expression Omnibus (GEO) to develop a metabolic prognostic signature associated with clinical and immune features in STAD using Cox regression analysis and least absolute shrinkage and selection operator (LASSO). The different proportions of immune cells and differentially expressed immune-related genes (DEIRGs) between high- and low-risk score groups based on the metabolic prognostic signature were evaluated to describe the association of cancer metabolism and immune response in STAD. A total of 883 metabolism-related genes in both TCGA and GEO databases were analyzed to obtain 184 differentially expressed metabolism-related genes (DEMRGs) between tumor and normal tissues. A 13-gene metabolic signature (GSTA2, POLD3, GLA, GGT5, DCK, CKMT2, ASAH1, OPLAH, ME1, ACYP1, NNMT, POLR1A, and RDH12) was constructed for prognostic prediction of STAD. Sixteen survival-related DEMRGs were significantly related to the overall survival of STAD and the immune landscape in the tumor microenvironment. Univariate and multiple Cox regression analyses and the nomogram proved that a metabolism-based prognostic risk score (MPRS) could be an independent risk factor. More importantly, the results were mutually verified using TCGA and GEO data. This study provided a metabolism-related gene signature for prognostic prediction of STAD and explored the association between metabolism and the immune microenvironment for future research, thereby furthering the understanding of the crosstalk between different molecular mechanisms in human STAD. Some prognosis-related metabolic pathways have been revealed, and the survival of STAD patients could be predicted by a risk model based on these pathways, which could serve as prognostic markers in clinical practice. Frontiers Media S.A. 2021-06-21 /pmc/articles/PMC8256842/ /pubmed/34235071 http://dx.doi.org/10.3389/fonc.2021.612952 Text en Copyright © 2021 Ye, Zheng, Zeng, Wei, Huang, Wang, Liu, Lin, Chen, Zheng and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ye, Zaisheng Zheng, Miao Zeng, Yi Wei, Shenghong Huang, He Wang, Yi Liu, Qinying Lin, Zhitao Chen, Shu Zheng, Qiuhong Chen, Luchuan A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title | A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title_full | A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title_fullStr | A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title_full_unstemmed | A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title_short | A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma |
title_sort | 13-gene metabolic prognostic signature is associated with clinical and immune features in stomach adenocarcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256842/ https://www.ncbi.nlm.nih.gov/pubmed/34235071 http://dx.doi.org/10.3389/fonc.2021.612952 |
work_keys_str_mv | AT yezaisheng a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zhengmiao a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zengyi a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT weishenghong a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT huanghe a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT wangyi a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT liuqinying a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT linzhitao a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT chenshu a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zhengqiuhong a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT chenluchuan a13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT yezaisheng 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zhengmiao 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zengyi 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT weishenghong 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT huanghe 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT wangyi 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT liuqinying 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT linzhitao 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT chenshu 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT zhengqiuhong 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma AT chenluchuan 13genemetabolicprognosticsignatureisassociatedwithclinicalandimmunefeaturesinstomachadenocarcinoma |