1. Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples
- Author
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Kinga Tóth, Sándor Spisák, Árpád V. Patai, Zsófia Brigitta Nagy, Alexandra Kalmár, Orsolya Galamb, Peter Igaz, Barbara Kinga Barták, Gábor Valcz, Béla Molnár, Zsolt Tulassay, Barnabás Wichmann, and Bálint Péterfia
- Subjects
Adenoma ,0301 basic medicine ,Cancer Research ,Colorectal cancer ,Nerve Tissue Proteins ,Colorectal adenoma ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,medicine ,Humans ,Epigenetics ,Liquid biopsy ,Promoter Regions, Genetic ,Molecular Biology ,Membrane Proteins ,Promoter ,Methylation ,DNA Methylation ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,CpG site ,030220 oncology & carcinogenesis ,DNA methylation ,Intercellular Signaling Peptides and Proteins ,Syndecan-2 ,Colorectal Neoplasms ,Research Paper - Abstract
Aberrant methylation is one of the most frequent epigenetic alterations that can contribute to tumor formation. Cell-free DNA can originate from tumor tissue; therefore, the evaluation of methylation markers in cell-free DNA can be a promising method for cancer screening. Our aim was to develop a panel of biomarkers with altered methylation along the colorectal adenoma-carcinoma sequence in both colonic tissue and plasma. Methylation of selected CpG sites in healthy colonic (n = 15), adenoma (n = 15), and colorectal cancer (n = 15) tissues was analyzed by pyrosequencing. MethyLight PCR was applied to study the DNA methylation of SFRP1, SFRP2, SDC2, and PRIMA1 gene promoters in 121 plasma and 32 biopsy samples. The effect of altered promoter methylation on protein expression was examined by immunohistochemistry. Significantly higher (P < 0.05) DNA methylation levels were detected in the promoter regions of all 4 markers, both in CRC and adenoma tissues compared with healthy controls. Methylation of SFRP1, SFRP2, SDC2, and PRIMA1 promoter sequences was observed in 85.1%, 72.3%, 89.4%, and 80.9% of plasma samples from patients with CRC and 89.2%, 83.8%, 81.1% and 70.3% from adenoma patients, respectively. When applied as a panel, CRC patients could be distinguished from controls with 91.5% sensitivity and 97.3% specificity [area under the curve (AUC) = 0.978], while adenoma samples could be differentiated with 89.2% sensitivity and 86.5% specificity (AUC = 0.937). Immunohistochemical analysis indicated decreasing protein levels of all 4 markers along the colorectal adenoma-carcinoma sequence. Our findings suggest that this methylation biomarker panel allows non-invasive detection of colorectal adenoma and cancer from plasma samples.
- Published
- 2017
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