Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas

Background: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. Methods SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (training set, n = 126; validation set, n = 73) and adjacent normal colonic tissues (n = 112). Results Mean immunohistochemistry scores in normal colonic tissues and tumors in a training set were as follows: normal colon, 24.2; hyperplastic polyp (HP), 21.6; SSL, 24.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 17.5; TSA, 7.3; low grade adenoma, 21.4; high grade adenoma, 11.7; high grade dysplasia (HGD), 12.1; EIC, 10.9. Abundant expression of SMOC1 in SSLs and significant downregulation of SMOC1 in TSAs were further confirmed in a validation set. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. Conclusion Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.