Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

BACKGROUND: To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the i...

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Autores principales: Yu, Fenglei, Huang, Xiaojie, Zhou, Danting, Zhao, Zhenyu, Wu, Fang, Qian, Banglun, Wang, Qiang, Chen, Juan, Liang, Qingchun, Jiang, Yi, Ding, Qi, He, Qiongzhi, Tang, Jingqun, Wang, Xiang, Liu, Wenliang, Chen, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824942/
https://www.ncbi.nlm.nih.gov/pubmed/36611170
http://dx.doi.org/10.1186/s13148-023-01422-y
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author Yu, Fenglei
Huang, Xiaojie
Zhou, Danting
Zhao, Zhenyu
Wu, Fang
Qian, Banglun
Wang, Qiang
Chen, Juan
Liang, Qingchun
Jiang, Yi
Ding, Qi
He, Qiongzhi
Tang, Jingqun
Wang, Xiang
Liu, Wenliang
Chen, Chen
author_facet Yu, Fenglei
Huang, Xiaojie
Zhou, Danting
Zhao, Zhenyu
Wu, Fang
Qian, Banglun
Wang, Qiang
Chen, Juan
Liang, Qingchun
Jiang, Yi
Ding, Qi
He, Qiongzhi
Tang, Jingqun
Wang, Xiang
Liu, Wenliang
Chen, Chen
author_sort Yu, Fenglei
collection PubMed
description BACKGROUND: To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment. METHODS: Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups. RESULTS: Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups. CONCLUSION: Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-023-01422-y.
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spelling pubmed-98249422023-01-08 Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer Yu, Fenglei Huang, Xiaojie Zhou, Danting Zhao, Zhenyu Wu, Fang Qian, Banglun Wang, Qiang Chen, Juan Liang, Qingchun Jiang, Yi Ding, Qi He, Qiongzhi Tang, Jingqun Wang, Xiang Liu, Wenliang Chen, Chen Clin Epigenetics Research BACKGROUND: To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment. METHODS: Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups. RESULTS: Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups. CONCLUSION: Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-023-01422-y. BioMed Central 2023-01-07 /pmc/articles/PMC9824942/ /pubmed/36611170 http://dx.doi.org/10.1186/s13148-023-01422-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yu, Fenglei
Huang, Xiaojie
Zhou, Danting
Zhao, Zhenyu
Wu, Fang
Qian, Banglun
Wang, Qiang
Chen, Juan
Liang, Qingchun
Jiang, Yi
Ding, Qi
He, Qiongzhi
Tang, Jingqun
Wang, Xiang
Liu, Wenliang
Chen, Chen
Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title_full Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title_fullStr Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title_full_unstemmed Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title_short Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
title_sort genetic, dna methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824942/
https://www.ncbi.nlm.nih.gov/pubmed/36611170
http://dx.doi.org/10.1186/s13148-023-01422-y
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