Large-scale integration of the non-coding RNAs with DNA methylation in human cancers

Sipeng Shen; Jiajin Chen; Hongru Li; Yunke Jiang; Yongyue Wei; Ruyang Zhang; Yang Zhao; Feng Chen

doi:10.1016/j.celrep.2023.112261

Large-scale integration of the non-coding RNAs with DNA methylation in human cancers

Cell Rep. 2023 Mar 28;42(3):112261. doi: 10.1016/j.celrep.2023.112261. Epub 2023 Mar 15.

Authors

Sipeng Shen¹, Jiajin Chen², Hongru Li³, Yunke Jiang³, Yongyue Wei⁴, Ruyang Zhang², Yang Zhao⁵, Feng Chen²

Affiliations

¹ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China; China International Cooperation Center of Environment and Human Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: sshen@njmu.edu.cn.
² Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
³ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
⁴ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; China International Cooperation Center of Environment and Human Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
⁵ Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Biomedical Big Data of Nanjing Medical University, Nanjing 211166, China. Electronic address: zhaoyang@njmu.edu.cn.

PMID: 36924495
DOI: 10.1016/j.celrep.2023.112261

Abstract

Characterizing influences of DNA methylation (DNAm) on non-coding RNAs (ncRNAs) is important to understand the mechanisms of gene regulation and cancer outcome. In our study, we describe the results of ncRNA quantitative trait methylation sites (ncQTM) analyses on 8,545 samples from The Cancer Genome Atlas (TCGA), 763 samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and 516 samples from Genotype-Tissue Expression (GTEx) to identify the significant associations between DNAm sites and ncRNAs (miRNA, long non-coding RNA [lncRNA], small nuclear RNA [snRNA], small nucleolar RNA [snoRNA], and rRNA) across 32 cancer types. With more than 22 billion tests, we identify 302,764 cis-ncQTMs (6.28% of all tested) and 79,841,728 trans-ncQTMs (1.15% of all tested). Most DNAm sites (70.6% on average) are in trans association, while only 25.2% DNAm sites are in cis association. Further, we develop a subtype named ncm_cluster based on cancer-specific ncRNAs thatis associated with tumor microenvironment, clinical outcome, and biological pathways. To comprehensively describe the ncQTM patterns, we developed a database named Pancan-ncQTM (http://bigdata.njmu.edu.cn/Pancan-ncQTM/).

Keywords: CP: Cancer; DNA methylation; multi-omics; non-coding RNA; overall survival; pan-cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation / genetics
Humans
MicroRNAs*
Neoplasms* / genetics
Proteomics
RNA, Long Noncoding* / genetics
RNA, Small Nucleolar
RNA, Untranslated / genetics
Tumor Microenvironment

Substances

RNA, Untranslated
MicroRNAs
RNA, Long Noncoding
RNA, Small Nucleolar