Prognostic significance of SOX17 and WNT5a promoter methylation status in circulating cell-free DNA metastatic colorectal cancer patients

Hippokratia. 2023 Jan-Mar;27(1):7-11.

Abstract

Aim: Carcinogenesis of colorectal cancer is a process involving genetic mutations and epigenetic alterations in its multiple phases. The most considerable epigenetic alteration occurring in colorectal cancer (CRC) tumorigenesis is the methylation-mediated silencing of tumor suppressor genes. The present study aimed to detect the methylation status of SOX17 and WNT5a promoters in cell-free DNA circulating in plasma of metastatic CRC patients and to investigate potential prognostic correlation.

Methods: A methylation-specific real-time polymerase chain reaction was utilized to investigate the methylation status of genes (SOX17 and WNT5a) promoter in the blood of 85 metastatic CRC patients.

Results: We found the SOX17 promoter methylated in 54/85 (63.5 %) while WNT5a was methylated in 39/85 (45.8 %) samples of the advanced CRC. All control samples were negative for SOX17 and WNT5a promoter methylation. Patients with metastatic CRC and methylated SOX17 and WNT5a promoter status had a significantly poorer outcome than patients with non-methylated ones.

Conclusions: Plasma SOX17 and WNT5a promoter methylation are frequent epigenetic events in advanced CRC. The reported correlations between the methylation status of genes (SOX17 and Wnt5a) promoter and poorer survival in patients with advanced CRC disease agree with the proposed role of SOX17 as a tumor suppressor gene. A more considerable CRC patient cohort is required to research these findings' potential further and investigate whether SOX17 in plasma could serve as a useful prognostic biomarker in metastatic CRC. HIPPOKRATIA 2023, 27 (1):7-11.

Keywords: DNA methylation; SOX17; WNT5a gene; cell-free DNA; metastatic colorectal cancer; prognosis.