Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance

Lingfang Feng; Tao Li; Biao Xu; Jing Huang; Hailing Xia; Zhaoqiang Jiang; Junfei Chen; Simiao Pan; Xing Zhang; Hua Jiang; Jianlin Lou

doi:10.1016/j.envpol.2024.124928

Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance

Environ Pollut. 2024 Sep 13:362:124928. doi: 10.1016/j.envpol.2024.124928. Online ahead of print.

Authors

Lingfang Feng¹, Tao Li², Biao Xu³, Jing Huang³, Hailing Xia¹, Zhaoqiang Jiang¹, Junfei Chen¹, Simiao Pan², Xing Zhang¹, Hua Jiang⁴, Jianlin Lou⁵

Affiliations

¹ School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China; Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A), Hangzhou Medical College, Hangzhou, Zhejiang, China.
² School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China.
³ School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China; School of Medicine, and The First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang, China.
⁴ Department of Otolaryngology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: zrjh@zju.edu.cn.
⁵ School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China; School of Medicine, and The First Affiliated Hospital, Huzhou University, Huzhou, Zhejiang, China. Electronic address: jianlinlou@163.com.

PMID: 39265763
DOI: 10.1016/j.envpol.2024.124928

Abstract

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulﬁte sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Keywords: Asbestos exposure; Circulating biomarkers; DNA methylation; Epigenetics; Malignant mesotheliomas.