Genome-Wide Analysis of DNA Methylation Identifies Two CpG Sites for the Early Screening of Colorectal Cancer

Abstract

Aim: To identify a panel of DNA methylation markers for the early diagnosis of colorectal cancer (CRC). Materials & methods: Using public omics data and our pyrosequencing data, we developed and validated a global methylation model and a CpG-methylation-based model for CRC screening. Results: Both of the models yielded high sensitivity and specificity for distinguishing CRC and its precursors (colorectal adenoma and colorectal laterally spreading tumor) from normal controls in eight independent datasets and our newly collected samples. More importantly, the two-CpG-based model showed high specificity in excluding inflammatory bowel diseases and other 13 cancer types. Conclusion: A diagnostic model based on two CpGs (cg09239744 and cg12587766) may be a powerful tool for CRC screening.

Keywords::

• colorectal adenoma
• colorectal cancer
• colorectal laterally spreading tumor
• diagnostic marker
• DNA methylation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0299

Author contributions

X Wu, M Feng and X Wang were responsible for the design of the study. X Wang performed the data analysis and drafted the manuscript. D Wang collected human colorectal samples and helped to analyze the data. H Zhang helped to check the data. X Wu, M Feng and H Zhang critically revised the manuscript. All the authors read and approved the final manuscript.

Acknowledgments

The authors thank TCGA, GEO, and ArrayExpress databases for their contribution. The authors also thank all patients who contributed samples for this study.

Financial & competing interests disclosure

This work was supported by National Natural Science Foundation of China (nos. 81770283 and 81473441), Health and Family Planning Commission of Hubei Province (no. WJ2017M249) and Clinical Medical Research Center of Peritoneal Cancer of Wuhan (no. 2015060911020462). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: 2015011).

Additional information

Funding

This work was supported by National Natural Science Foundation of China (nos. 81770283 and 81473441), Health and Family Planning Commission of Hubei Province (no. WJ2017M249) and Clinical Medical Research Center of Peritoneal Cancer of Wuhan (no. 2015060911020462). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.