Hypermethylation of PDX1, EN2, and MSX1 predicts the prognosis of colorectal cancer

Abstract

Despite numerous observations regarding the relationship between DNA methylation changes and cancer progression, only a few genes have been verified as diagnostic biomarkers of colorectal cancer (CRC). To more practically detect methylation changes, we performed targeted bisulfite sequencing. Through co-analysis of RNA-seq, we identified cohort-specific DNA methylation markers: CpG islands of the intragenic regions of PDX1, EN2, and MSX1. We validated that these genes have oncogenic features in CRC and that their expression levels are increased in correlation with the hypermethylation of intragenic regions. The reliable depth of the targeted bisulfite sequencing data enabled us to design highly optimized quantitative methylation-specific PCR primer sets that can successfully detect subtle changes in the methylation levels of candidate regions. Furthermore, these methylation levels can divide CRC patients into two groups denoting good and poor prognoses. In this study, we present a streamlined workflow for screening clinically significant differentially methylated regions. Our discovery of methylation markers in the PDX1, EN2, and MSX1 genes suggests their promising performance as prognostic markers and their clinical application in CRC patients. Cancer: Mapping malignant modifications An experimental strategy for detecting patterns of DNA modification reveals gene-specific alterations associated with worse outcomes in colorectal cancer patients. Many genomic regions undergo a process of chemical modification called methylation, which can strongly affect the expression of nearby genes. Many cancers exhibit abnormal methylation, and South Korean researchers led by Tae-You Kim of Seoul National University and Lark Kyun Kim of Yonsei University College of Medicine, Seoul, have developed a strategy for identifying such tumor-specific modifications. They identified a trio of genes that undergo excessive methylation in colorectal cancer, and show that this 'signature' is associated with more advanced metastatic tumors and shorter overall survival. The results from this study could give clinicians an additional diagnostic tool, and highlight the potential utility of performing such methylation profiling in other cancer types.