Department of Molecular Biology, Sapporo Medical University School of Medicine, S1, W17, Chuo-Ku, Sapporo, 060-8556, Japan.
Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.
BMC Gastroenterol. 2024 Mar 1;24(1):91. doi: 10.1186/s12876-024-03175-1.
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.
SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112).
SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. 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.
Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.
结直肠锯齿状病变中存在异常的 DNA 甲基化。我们之前报道过,SMOC1 的 CpG 岛在传统锯齿状腺瘤(TSA)和结直肠癌(CRC)中经常发生甲基化,但在无蒂锯齿状病变(SSL)中很少发生甲基化。在本研究中,我们旨在进一步研究 SMOC1 在早期结直肠病变中的表达特征。
我们对一系列结直肠肿瘤(n=199)和相邻正常结肠组织(n=112)进行了 SMOC1 免疫组织化学分析。
SMOC1 在正常结肠和 SSL 中大量表达,而在 TSA、高级别腺瘤和癌症中则显著下调。平均免疫组化评分如下:正常结肠 24.2;增生性息肉(HP)18.9;SSL 23.8;SSL 伴异型增生(SSLD)/SSL 伴早期浸润癌(EIC)15.8;TSA 5.4;TSA 伴高级别异型增生(HGD)/EIC 4.7;非高级别腺瘤 21.4;高级别腺瘤 11.9;EIC 10.9。SMOC1 表达水平较高与近端结肠位置和平坦的肿瘤形态呈正相关,反映了其在 SSL 中的大量表达。在包含扁平成分和外生成分的 TSA 中,SMOC1 的表达水平在外生成分中显著降低。
我们的结果表明,SMOC1 的表达减少与 TSA 和传统腺瘤的进展有关,SMOC1 的表达可能是锯齿状病变和结直肠肿瘤风险预测的诊断标志物。