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

Clinical Epigenetics

Research

Xiaojie Huang¹  Fang Wu²  Yi Jiang³  Qingchun Liang³  Juan Chen⁴  Jingqun Tang⁵  Danting Zhou⁵  Xiang Wang⁵  Chen Chen⁵  Zhenyu Zhao⁵  Banglun Qian⁵  Fenglei Yu⁵  Wenliang Liu⁵  Qiang Wang⁵  Qiongzhi He⁶  Qi Ding⁶ 

[1] Department of Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;Department of Oncology, Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;Department of Pathology, Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, People’s Republic of China;Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China;Geneplus-Beijing Institute, Beijing, People’s Republic of China;

关键词: Synchronous multiple primary lung cancers;    Gene mutation;    DNA methylation;    Immune profile;    Tumor microenvironment;   

DOI  :  10.1186/s13148-023-01422-y

 received in 2022-07-30, accepted in 2023-01-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTo 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.MethodsHundred 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.ResultsLesions 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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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