Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Aberrant DNA methylation plays a critical role in the developmentand progression of colorectal cancer (CRC), which hashigh incidence and mortality rates in Korea. Various CRC-associatedmethylation markers for cancer diagnosis and prognosishave been developed; however, they have not been validatedfor Korean patients owing to the lack of comprehensive clinicaland methylome data. Here, we obtained reliable methylationprofiles for 228 tumor, 103 adjacent normal, and two unmatchednormal colon tissues from Korean patients with CRCusing an Illumina Infinium EPIC array; the data were correctedfor biological and experiment biases. A comparative methylomeanalysis confirmed the previous findings that hypermethylatedpositions in the tumor were highly enriched in CpG island andpromoter, 5’ untranslated, and first exon regions. However,hypomethylated positions were enriched in the open-sea regionsconsiderably distant from CpG islands. After applying a CpGisland methylator phenotype (CIMP) to the methylome data oftumor samples to stratify the CRC patients, we consolidatedthe previously established clinicopathological findings that thetumors with high CIMP signatures were significantly enrichedin the right colon. The results showed a higher prevalence ofmicrosatellite instability status and MLH1 methylation in tumorswith high CMP signatures than in those with low or non-CIMPsignatures. Therefore, our methylome analysis and dataset provideinsights into applying CRC-associated methylation markersfor Korean patients regarding cancer diagnosis and prognosis.
Abstract
Aberrant DNA methylation plays a critical role in the developmentand progression of colorectal cancer (CRC), which hashigh incidence and mortality rates in Korea. Various CRC-associatedmethylation markers for cancer diagnosis and prognosishave been developed; however, they have not been validatedfor Korean patients owing to the lack of comprehensive clinicaland methylome data. Here, we obtained reliable methylationprofiles for 228 tumor, 103 adjacent normal, and two unmatchednormal colon tissues from Korean patients with CRCusing an Illumina Infinium EPIC array; the data were correctedfor biological and experiment biases. A comparative methylomeanalysis confirmed the previous findings that hypermethylatedpositions in the tumor were highly enriched in CpG island andpromoter, 5’ untranslated, and first exon regions. However,hypomethylated positions were enriched in the open-sea regionsconsiderably distant from CpG islands. After applying a CpGisland methylator phenotype (CIMP) to the methylome data oftumor samples to stratify the CRC patients, we consolidatedthe previously established clinicopathological findings that thetumors with high CIMP signatures were significantly enrichedin the right colon. The results showed a higher prevalence ofmicrosatellite instability status and MLH1 methylation in tumorswith high CMP signatures than in those with low or non-CIMPsignatures. Therefore, our methylome analysis and dataset provideinsights into applying CRC-associated methylation markersfor Korean patients regarding cancer diagnosis and prognosis.
참고문헌 (32)
- Das PM, "DNA methylation and cancer", J Clin Oncol, 22, pp.4632~4642 (2004)
- Lakshminarasimhan R, "The role of DNA methylation in cancer", Adv Exp Med Biol, 945, pp.151~172 (2016)
- Nishiyama A, "Navigating the DNA methylation landscape of cancer", Trends Genet, 37, pp.1012~1027 (2021)
- Herman JG, "Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma", Proc Natl Acad Sci U S A, 95, pp.6870~6875 (1998)
- Zhao P, "Mismatch repair deficiency", microsatellite instability-high as a predictor for anti-PD-1, J Hematol Oncol, pp.2019, 12[DOI]
- Zlobec I, "Comprehensive analysis of CpG island methylator phenotype(CIMP)-high, -low, and-negative colorectal cancers based on protein marker expression and molecular features", J Pathol, 225, pp.336~343 (2011)
- Nazemalhosseini Mojarad E, "The CpG island methylator phenotype(CIMP)in colorectal cancer", Gastroenterol Hepatol Bed Bench, 6, pp.120~128 (2013)
- Guinney J, "The consensus molecular subtypes of colorectal cancer", Nat Med, 21, pp.1350~1356 (2015)
- Singh MP, "Molecular subtypes of colorectal cancer : an emerging therapeutic opportunity for personalized medicine", Genes Dis, 8, pp.133~145 (2021)
- Joe S, "Epigenetic insights into colorectal cancer : comprehensive genome-wide DNA methylation profiling of 294 patients in Korea", BMB Rep, 56, pp.563~568 (2023)
- Galanter JM, "Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures", eLife, 6, pp.e20532~ (2017)
- Jeon SA, "Genomic and transcriptomic analysis of Korean colorectal cancer patients", Genes Genomics, 44, pp.967~979 (2022)
- Lee SH, "Landscape of actionable genetic alterations profiled from 1, 071 tumor samples in Korean cancer patients", Cancer Res Treat, 51, pp.211~222 (2019)
- Yang X, "Gene body methylation can alter gene expression and is a therapeutic target in cancer", Cancer Cell, 26, pp.577~590 (2014)
- McInnes T, "Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer", BMC Cancer, 17, pp.228~ (2017)
- Silva AL, "Boosting Wnt activity during colorectal cancer progression through selective hypermethylation of Wnt signaling antagonists", BMC Cancer, 14, pp.891~ (2014)
- Guo X, "Signaling cross-talk between TGF-beta", BMP and other pathways, 2009, pp.19, 71~88
- Huang F, "Regulation of TGF-beta receptor activity", Cell Biosci, 2, pp.9~ (2012)
- Ding N, "Correlation between SMADs and colorectal cancer expression, prognosis, and immune infiltrates", Int J Anal Chem, 2023, pp.8414040~ (2023)
- Hata A, "TGF-beta signaling from receptors to Smads", Cold Spring Harb Perspect Biol, 8, pp.a022061~ (2016)
- Wagstaff L, "The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis", Front Biosci(Landmark Ed), 16, pp.1861~1872 (2011)
- Choi JE, "Aberrant methylation of ADAMTS1 in non-small cell lung cancer", Cancer Genet Cytogenet, 187, pp.80~84 (2008)
- Lind GE, "ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis", Cell Oncol, 28, pp.259~272 (2006)
- Cal S, "ADAMTS proteases and cancer", Matrix Biol 44-46 (2015)
- Hibi K, "Methylation pattern of CDH13 gene in digestive tract cancers", Br J Cancer, 91, pp.1139~1142 (2004)
- Yan H, "Identifying CpG sites with different differential methylation frequencies in colorectal cancer tissues based on individualized differential methylation analysis", Oncotarget, 8, pp.47356~47364 (2017)
- Zhang Y, "GNG7 and ADCY1as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma through bioinformatic-based analyses", Sci Rep, 11, pp.20441~ (2021)
- Fan Y, "Epigenetic identification of ADCY4 as a biomarker for breast cancer : an integrated analysis of adenylate cyclases", Epigenomics, 11, pp.1561~1579 (2019)
- Jass JR, "Classification of colorectal cancer based on correlation of clinical, morphological and molecular features", Histopathology, 50, pp.113~130 (2007)
- Sugai T, "Analysis of molecular alterations in left-and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis : proposal for new molecular profile of colorectal carcinomas", J Mol Diagn, 8, pp.193~201 (2006)
- Petrelli F, "Prognostic survival associated with left-sided vs right-sided colon cancer : a systematic review and meta-analysis", JAMA Oncol, 3, pp.211~219 (2017)
- Lee B, "Introduction of the Korea BioData Station(K-BDS)for sharing biological data", Genomics Inform, 21, pp.e12~ (2023)