Article Abstract

Identification the potential of stool-based SNCA methylation as a candidate biomarker for early colorectal cancer detection

Authors: Qinglan Yang, Shuiming Wang, Jiong Ma, Xiaowei Li, Xu Liu, Mengna Peng, Guangjie Liu, Yaping Wang, Heiying Jin, Yimei Fan


Background: Stool-based DNA methylation are emerging as promising biomarkers for colorectal cancer (CRC), but their capability for detecting curable stages (adenomas) remains unclear. This study aims to explore the potential of selected candidate biomarkers (SNCA, SPG20 and FBN1) in stool samples for identifying patients with adenomas or CRC.
Methods: Thirty-one patients with CRC, 49 patients with adenomas, and 64 normal controls were selected. Stool samples were processed by the stool intestinal mucosal cells collector and analyzed by quantitative methylation-specific polymerase chain reaction (qMSP).
Results: Promoter methylation status of genes was denoted as percentage of methylated reference (PMR) values. The SNCA PMR values were significantly higher in CRC and adenomas groups than normal controls. The area under the ROC curve (AUC) for SNCA was 0.836 and 0.772 for detection of CRC and adenomas, respectively. The sensitivity of stool-based SNCA methylation was 83.9% for CRC and 75.5% for adenomas, with the specificity of 75% for both. The odds ratio (OR) for CRC and adenomas with stool SNCA hypermethylation was 11.291 and 9.234, respectively, after adjustment for patients’ age and sex. Though there was a trend of increase of SNCA promoter methylation with disease progression, the difference was not significant. No significant difference in stool-based SNCA methylation was found between proximal and distal lesions. SNCA methylation significantly reduced after tumor resection compared to the initial status. The SPG20 and FBN1 methylation status was not significantly different among groups.
Conclusions: The results validated the capability of SNCA methylation in stool samples for the identification of patients with adenomas or CRC.