Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China
Received 2 September 2018
Accepted for publication 5 May 2019
Published 28 June 2019 Volume 2019:11 Pages 5785—5797
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Beicheng Sun
Wei-Min Xiong,1 Qiu-Ping Xu,1 Ren-Dong Xiao,2 Zhi-Jian Hu,2 Lin Cai,1,3–5 Fei He1,3–5
1Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350108, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 3Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, People’s Republic of China; 4Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, People’s Republic of China; 5Fujian Provincial Key Laboratory of Environment Factors and Cancer, Fujian Medical University, Fuzhou 350108, People’s Republic of China
Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses.
Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles.
Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues.
Conclusion: Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.
Keywords: lung neoplasms, chlamydia pneumonia, DNA methylation, gene expression
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