Evidence of origin with epigenetic change of metachronous lesions in early gastric cancer after endoscopic submucosal dissection

Abstract Early gastric cancer (EGC) with metachronous lesions developing on scars after endoscopic submucosal dissection (ESD) is extremely rare and hard to treat. We evaluated whether DNA methylation of the cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), would predict such lesions. CDO1 methylation (TaqMeth) values were compared between 11 patients with metachronous lesions developing on scars after ESD (M group) identified from 2,055 patients (0.5%) and 33 patients with EGC with no confirmed evidence of metachronous lesions at > 3 years after ESD (solitary [S] group). To assess Helicobacter pylori influence, 11 H. pylori-negative EGC patients (N group) were also analyzed. Each ESD specimen was measured at the tumor (T) and 4-points separated tumor-adjacent noncancerous mucosa (TAM). TaqMeth values for T were significantly higher than TAM (S + M) (P = 0.0019) and TAM (N) (P < 0.0001). Moreover, TAM (M) had significantly higher TaqMeth values than TAM (S) (P < 0.0001) suggesting that TAM (M) exhibited CDO1 hypermethylation similar to T (P = 0.5713). Additionally, TaqMeth values for TAM (S) were significantly higher than TAM (N) (P < 0.0001). The receiver operating characteristic for discriminating the highest TaqMeth values separated TAMs (M) from those of TAMs (S) was 0.81. CDO1 hypermethylation promisingly predicted EGC with metachronous lesions developing on scars after ESD.