Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Autor:	Talukdar FR; International Agency for Research on Cancer, Lyon, France. fazlur08@gmail.com hercegz@iarc.fr., Soares Lima SC; Department of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, Brazil., Khoueiry R; International Agency for Research on Cancer, Lyon, France., Laskar RS; International Agency for Research on Cancer, Lyon, France., Cuenin C; International Agency for Research on Cancer, Lyon, France., Sorroche BP; International Agency for Research on Cancer, Lyon, France.; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Boisson AC; International Agency for Research on Cancer, Lyon, France., Abedi-Ardekani B; International Agency for Research on Cancer, Lyon, France., Carreira C; International Agency for Research on Cancer, Lyon, France., Menya D; Moi University, Eldoret, Kenya., Dzamalala CP; University of Malawi, Blantyre, Malawi., Assefa M; Addis Ababa University, Addis Ababa, Ethiopia., Aseffa A; Armauer Hansen Research Institute, Addis Ababa, Ethiopia., Miranda-Gonçalves V; Department of Pathology and Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto and Biomedical Sciences Institute of University of Porto, Porto, Portugal., Jerónimo C; Department of Pathology and Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto and Biomedical Sciences Institute of University of Porto, Porto, Portugal., Henrique RM; Department of Pathology and Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto and Biomedical Sciences Institute of University of Porto, Porto, Portugal., Shakeri R; Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Malekzadeh R; Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Gasmelseed N; Department of Molecular Biology, National Cancer Institute, University of Gezira, Gezira, Sudan., Ellaithi M; Department of Histopathology and Cytology, Al-Neelain University, Khartoum, Sudan., Gangane N; Mahatma Gandhi Institute of Medical Sciences, Sevagram, India., Middleton DRS; International Agency for Research on Cancer, Lyon, France., Le Calvez-Kelm F; International Agency for Research on Cancer, Lyon, France., Ghantous A; International Agency for Research on Cancer, Lyon, France., Roux ML; International Agency for Research on Cancer, Lyon, France., Schüz J; International Agency for Research on Cancer, Lyon, France., McCormack V; International Agency for Research on Cancer, Lyon, France., Parker MI; Integrative Biomedical Sciences and IDM, University of Cape Town, Cape Town, South Africa., Pinto LFR; Department of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, Brazil., Herceg Z; International Agency for Research on Cancer, Lyon, France. fazlur08@gmail.com hercegz@iarc.fr.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2021 May 15; Vol. 81 (10), pp. 2612-2624. Date of Electronic Publication: 2021 Mar 19.
DOI:	10.1158/0008-5472.CAN-20-3445
Abstrakt:	Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2 , and THSD4 , had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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