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Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. Thi...

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Autores principales: Zhou, Ning, Tang, Quanying, Yu, Haochuan, Li, Tong, Ren, Fan, Zu, Lingling, Chen, Gang, Chen, Jun, Xu, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699278/
https://www.ncbi.nlm.nih.gov/pubmed/36438661
http://dx.doi.org/10.3389/fmolb.2022.1034208
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author Zhou, Ning
Tang, Quanying
Yu, Haochuan
Li, Tong
Ren, Fan
Zu, Lingling
Chen, Gang
Chen, Jun
Xu, Song
author_facet Zhou, Ning
Tang, Quanying
Yu, Haochuan
Li, Tong
Ren, Fan
Zu, Lingling
Chen, Gang
Chen, Jun
Xu, Song
author_sort Zhou, Ning
collection PubMed
description Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. This study aims to evaluate the prognostic value of 1C metabolism-related genes in LUAD and to explore the potential correlation of these genes with gene methylation, the tumor microenvironment, and immunotherapy. Methods: We identified 26 1C metabolism-related genes and performed a Kaplan-Meier and Cox regression analysis to evaluate the prognostic value of these genes. Consensus clustering was further performed to determine the 1C metabolism-related gene patterns in LUAD. The clinical and molecular characteristics of subgroups were investigated based on consensus clustering. CIBERSORT and ssGSEA algorithms were used to calculate the relative infiltration levels of multiple immune cell subsets. The relationship between 1C metabolism-related genes and drug sensitivity to immunotherapy was evaluated using the CellMiner database and IMvigor210 cohort, respectively. Results: The expression levels of 23 1C metabolism-related genes were significantly different between LUAD tumor tissues and normal tissues. Seventeen of these genes were related to prognosis. Two clusters (cluster 1 and cluster 2) were identified among 497 LUAD samples based on the expression of 7 prognosis-related genes. Distinct expression patterns were observed between the two clusters. Compared to cluster 2, cluster 1 was characterized by inferior overall survival (OS) (median OS = 41 vs. 60 months, p = 0.00031), increased tumor mutation burden (15.8 vs. 7.5 mut/Mb, p < 0.001), high expression of PD-1 (p < 0.001) and PD-L1 (p < 0.001), as well as enhanced immune infiltration. 1C metabolism-related genes were positively correlated with the expression of methylation enzymes, and a lower methylation level was observed in cluster 1 (p = 0.0062). Patients in cluster 1 were resistant to chemotherapy drugs including pemetrexed, gemcitabine, paclitaxel, etoposide, oxaliplatin, and carboplatin. The specific expression pattern of 1C metabolism-related genes was correlated with a better OS in patients treated with immunotherapy (median OS: 11.2 vs. 7.8 months, p = 0.0034). Conclusion: This study highlights that 1C metabolism is correlated with the prognosis of LUAD patients and immunotherapy efficacy. Our findings provide novel insights into the role of 1C metabolism in the occurrence, development, and treatment of LUAD, and can assist in guiding immunotherapy for LUAD patients.
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spelling pubmed-96992782022-11-26 Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma Zhou, Ning Tang, Quanying Yu, Haochuan Li, Tong Ren, Fan Zu, Lingling Chen, Gang Chen, Jun Xu, Song Front Mol Biosci Molecular Biosciences Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. This study aims to evaluate the prognostic value of 1C metabolism-related genes in LUAD and to explore the potential correlation of these genes with gene methylation, the tumor microenvironment, and immunotherapy. Methods: We identified 26 1C metabolism-related genes and performed a Kaplan-Meier and Cox regression analysis to evaluate the prognostic value of these genes. Consensus clustering was further performed to determine the 1C metabolism-related gene patterns in LUAD. The clinical and molecular characteristics of subgroups were investigated based on consensus clustering. CIBERSORT and ssGSEA algorithms were used to calculate the relative infiltration levels of multiple immune cell subsets. The relationship between 1C metabolism-related genes and drug sensitivity to immunotherapy was evaluated using the CellMiner database and IMvigor210 cohort, respectively. Results: The expression levels of 23 1C metabolism-related genes were significantly different between LUAD tumor tissues and normal tissues. Seventeen of these genes were related to prognosis. Two clusters (cluster 1 and cluster 2) were identified among 497 LUAD samples based on the expression of 7 prognosis-related genes. Distinct expression patterns were observed between the two clusters. Compared to cluster 2, cluster 1 was characterized by inferior overall survival (OS) (median OS = 41 vs. 60 months, p = 0.00031), increased tumor mutation burden (15.8 vs. 7.5 mut/Mb, p < 0.001), high expression of PD-1 (p < 0.001) and PD-L1 (p < 0.001), as well as enhanced immune infiltration. 1C metabolism-related genes were positively correlated with the expression of methylation enzymes, and a lower methylation level was observed in cluster 1 (p = 0.0062). Patients in cluster 1 were resistant to chemotherapy drugs including pemetrexed, gemcitabine, paclitaxel, etoposide, oxaliplatin, and carboplatin. The specific expression pattern of 1C metabolism-related genes was correlated with a better OS in patients treated with immunotherapy (median OS: 11.2 vs. 7.8 months, p = 0.0034). Conclusion: This study highlights that 1C metabolism is correlated with the prognosis of LUAD patients and immunotherapy efficacy. Our findings provide novel insights into the role of 1C metabolism in the occurrence, development, and treatment of LUAD, and can assist in guiding immunotherapy for LUAD patients. Frontiers Media S.A. 2022-11-11 /pmc/articles/PMC9699278/ /pubmed/36438661 http://dx.doi.org/10.3389/fmolb.2022.1034208 Text en Copyright © 2022 Zhou, Tang, Yu, Li, Ren, Zu, Chen, Chen and Xu. 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 Molecular Biosciences
Zhou, Ning
Tang, Quanying
Yu, Haochuan
Li, Tong
Ren, Fan
Zu, Lingling
Chen, Gang
Chen, Jun
Xu, Song
Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title_full Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title_fullStr Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title_full_unstemmed Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title_short Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
title_sort comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699278/
https://www.ncbi.nlm.nih.gov/pubmed/36438661
http://dx.doi.org/10.3389/fmolb.2022.1034208
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