Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
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Published:2023-01-07
Issue:1
Volume:15
Page:
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ISSN:1868-7083
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Container-title:Clinical Epigenetics
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language:en
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Short-container-title:Clin Epigenet
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
Abstract
Abstract
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.
Funder
Hunan Provincial Key Area R&D Program
Natural Science Foundation of Hunan Province
Natural Science Foundation of Hunan Province
CSCO Cancer Research Foundation
Changsha Municipal Natural Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
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