Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC),and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealeda significant presence of hypomethylated probes, primarilywithin the gene body regions; few hypermethylated sites wereobserved, which were mostly enriched in promoter-like andCpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatelliteinstability-high (MSI-H). Additionally, our findings indicated asignificant correlation between methylation of the MLH1 geneand MSI-H status. Furthermore, we found that the CIMP-H hada higher tendency to affect the right-side of the colon tissuesand was slightly more prevalent among older patients. Throughour methylome profile analysis, we successfully verified themethylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundationfor exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.
Abstract
Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC),and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealeda significant presence of hypomethylated probes, primarilywithin the gene body regions; few hypermethylated sites wereobserved, which were mostly enriched in promoter-like andCpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatelliteinstability-high (MSI-H). Additionally, our findings indicated asignificant correlation between methylation of the MLH1 geneand MSI-H status. Furthermore, we found that the CIMP-H hada higher tendency to affect the right-side of the colon tissuesand was slightly more prevalent among older patients. Throughour methylome profile analysis, we successfully verified themethylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundationfor exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.
참고문헌 (29)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Goel A, "Epigenetics of colorectal cancer", Gastroenterology, 143, pp.1442~1460 (2012)
- Sun D, "Influence of the microbiota on epigenetics in colorectal cancer", Natl Sci Rev, 6, pp.1138~1148 (2019)
- Esteban-Gil A, "ColPortal, an integrative multiomic platform for analysing epigenetic interactions in colorectal cancer", Sci Data, 6, pp.255~ (2019)
- Ng JM, "Promoter hypermethylation of tumour suppressor genes as potential biomarkers in colorectal cancer", Int J Mol Sci, 16, pp.2472~2496 (2015)
- Fatemi N, "DNA methylation biomarkers in colorectal cancer : clinical applications for precision medicine", Int J Cancer, 151, pp.2068~2081 (2022)
- Jung G, "Epigenetics of colorectal cancer : biomarker and therapeutic potential", Nat Rev Gastroenterol Hepatol, 17, pp.111~130 (2020)
- Cunningham JM, "Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability", Cancer Res, 58, pp.3455~3460 (1998)
- Popat S, "Systematic review of microsatellite instability and colorectal cancer prognosis", J Clin Oncol, 23, pp.609~618 (2005)
- Issa JP, "CpG island methylator phenotype in cancer", Nat Rev Cancer, 4, pp.988~993 (2004)
- Jones PA, "The fundamental role of epigenetic events in cancer", Nat Rev Genet, 3, pp.415~428 (2002)
- Toyota M, "CpG island methylator phenotype in colorectal cancer", Proc Natl Acad Sci U S A, 96, pp.8681~8686 (1999)
- Mojarad EN, "The CpG island methylator phenotype(CIMP)in colorectal cancer", Gastroenterol Hepatol Bed Bench, 6, pp.120~128 (2013)
- Weisenberger DJ, "CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer", Nat Genet, 38, pp.787~793 (2006)
- Ahn JB, "DNA methylation predicts recurrence from resected stage III proximal colon cancer", Cancer, 117, pp.1847~1854 (2011)
- Rhee YY, "Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas depend on L1 methylation level", Ann Surg Oncol, 19, pp.3441~3448 (2012)
- Leek JT, "The sva package for removing batch effects and other unwanted variation in high-throughput experiments", Bioinformatics, 28, pp.882~883 (2012)
- Maksimovic J, "SWAN : subset-quantile within array normalization for Illumina Infinium HumanMethylation450 BeadChips", Genome Biol, 13, pp.R44~ (2012)
- Aryee MJ, "Minfi : a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays", Bioinformatics, 30, pp.1363~1369 (2014)
- Ritchie ME, "limma powers differential expression analyses for RNA-sequencing and microarray studies", Nucleic Acids Res, 43, pp.e47~ (2015)
- Sheaffer KL, "DNA hypomethylation contributes to genomic instability and intestinal cancer initiation", Cancer Prev Res(Phila), 9, pp.534~546 (2016)
- McInnes T, "Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer", BMC Cancer, 17, pp.228~ (2017)
- Muller D, "DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer", Biochim Biophys Acta Rev Cancer, 1877, pp.188722~ (2022)
- Worthley DL, "Colorectal cancer : molecular features and clinical opportunities", Clin Biochem Rev, 31, pp.31~38 (2010)
- Jia M, "Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer : a systematic review", Clin Epigenetics, 8, pp.25~ (2016)
- Inamura K, "Tumor LINE-1 methylation level and microsatellite instability in relation to colorectal cancer prognosis", J Natl Cancer Inst 106 (2014)
- Hur H, "Characteristics and survival of Korean patients with colorectal cancer based on data from the Korea Central Cancer Registry Data", Ann Coloproctol, 34, pp.212~221 (2018)
- Baek SK, "Clinical characteristics and survival of colorectal cancer patients in Korea stratified by age", Korean J Int Med, 36, pp.985~991 (2021)
- Lee B, "Introduction of the Korea BioData Station(K-BDS)for sharing biological data", Genomics Inf, 21, pp.e12~ (2023)