Aberrant methylation of CDKN2A, RASSF1A and WIF1 in sporadic adenocarcinomatous colorectal cancer: Associations with clinicopathological features

Accumulating evidence support that aberrant methylation of various cancer-related genes plays an important role in the initiation and progression of colorectal cancer (CRC). This study aims to validate the accuracy of methylation specific polymerase chain reaction (MSP) to assess frequency and distribution of GSTP1, CDKN2A, RASSF1A, and WIF1 methylation and analyse their correlation with clinicopathological variables in sporadic adenocarcinomatous CRC. Of the 248 CRC tissues, methylation was identified in 7.7% for GSTP1, 22.2% for CDKN2A, 33.1% for RASSF1A, and 54.4% for WIF1. Hypermethylation of CDKN2A, RASSF1A, and WIF1 was significantly associated with adenocarcinoma (p< 0.001), mucinous adenocarcinoma (p< 0.001), and signet-ring cell adenocarcinoma subtypes (p = 0.017), respectively. Both CDKN2A and WIF1 methylations were more common in stage II (p = 0.012 for CDKN2A and p = 0.010 for WIF1) and absence of lymph node metastasis (p = 0.011 for CDKN2A and p = 0.012 for WIF1) but were less common in stage III (p = 0.016 for CDKN2A and p = 0.010 for WIF1). RASSF1A methylation was associated with moderate differentiation (p = 0.038). These findings suggest that methylation of CDKN2A, RASSF1A, and WIF1 may significantly contribute to CRC pathogenesis and may be considered as valuable biomarkers for accessing the development and progression of particular subtypes of colorectal cancer.