Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer

Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-de...

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Published inScientific reports Vol. 13; no. 1; p. 15401
Main Authors Bao-Caamano, Aida, Costa-Fraga, Nicolás, Cayrefourcq, Laure, Jácome, María Amalia, Rodriguez-Casanova, Aitor, Muinelo-Romay, Laura, López-López, Rafael, Alix-Panabières, Catherine, Díaz-Lagares, Angel
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.09.2023
Nature Publishing Group
Nature Portfolio
Subjects
631/67/322
692/4028/67
Cancer
Colorectal cancer
Colorectal carcinoma
CpG islands
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Gene regulation
Humanities and Social Sciences
Metastases
Metastasis
multidisciplinary
Science
Science (multidisciplinary)
Solid tumors
Therapeutic targets
Tumor cells
Wnt protein
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Summary:Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional profile of CTC-MCC-41 was also evaluated. Differentially methylated CpGs were validated with pyrosequencing and qMSP. Compared to primary and metastatic CRC cells, the methylation profile of CTC-MCC-41 was globally different and characterized by a slight predominance of hypomethylated CpGs mainly distributed in CpG-poor regions. Promoter CpG islands and shore regions of CTC-MCC-41 displayed a unique methylation profile that was associated with the transcriptional program and relevant cancer pathways, mainly Wnt signaling. The epigenetic regulation of relevant genes in CTC-MCC-41 was validated. This study provides new insights into the epigenomic landscape of metastasis-competent CTCs, revealing biological information for metastasis development, as well as new potential biomarkers and therapeutic targets for CRC patients.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-42037-w