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

Yeongun Lee, So Hee Dho, Jiyeon Lee, Ji Hyun Hwang, Minjung Kim, Won Young Choi, Jin Young Lee, Jongwon Lee, Woochul Chang, Min Young Lee, Jungmin Choi, Tae You Kim, Lark Kyun Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)156-168
Number of pages13
JournalExperimental and Molecular Medicine
Volume54
Issue number2
DOIs
Publication statusPublished - 2022 Feb

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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