Table 1.
Clinicopathological features of the patients according to CIMP status.
Fig 1.
Relationship between CIMP and MLH1 methylation.
a) Tile map showing methylation pattern. Twenty eight loci (APC, CACNA1G, CHFR, COX2, DAPK, DCC, HPP1, MGMT-Mp region, MGMT-Eh region, MINT1, MINT2, MINT31, MLH1 5', MLH1 3', p14, p16, RASSF1A, RASSF2A-region1, RASSF2A-region2, RASSF3, RASSF5, RASSF6, RUNX3, SFRP2-region1, SFRP2-region2, UNC5C, 3OST2, FOXL2) were analyzed to determine CIMP status. Thirty patients with not less than ten methylated loci were identified as the CIMP-high group. b) Venn diagram showing the overlap of MLH1 3' methylation and CIMP status. The overlapping relationship between MLH1 3' methylation and CIMP status was analyzed. 10 patients were in the combined in the CIMP-high/MLH1 3' methylated (A), 1 patients were in the CIMP-low/MLH1 3' methylated (B), 20 patients were in the CIMP high/MLH1 3' non-methylated (C), and 37 patients were in the CIMP-low/MLH1 3' non-methylated groups (D). c) Kaplan–Meier estimate of OS in patients with MLH1 3' methylated or non-methylated gastric cancers. Kaplan–Meier survival curves were generated according to MLH1 3' methylation status. The 5-year survival rates were analyzed for the MLH1 3' methylated and non-methylated groups. The survival rate was significantly higher in the MLH1 3' methylated group than in the non-methylated group (log-rank P = 0.0257). d) Kaplan–Meier estimate of OS in patients with CIMP-high or CIMP-low gastric cancers. Kaplan–Meier survival curves were generated according to CIMP status. The 5-year survival rate was analyzed for the CIMP-high group and CIMP-low group. The survival rate was slightly higher in the CIMP-high group than in the CIMP-low group, but the difference was not significant (log-rank P = 0.0688). e) Contribution of CIMP and mismatch repair deficiency status to survival rate. Kaplan–Meier survival curves were generated according to CIMP and MLH1 methylation status. The patients were classified on the basis of combined CIMP status and MLH1 methylation status into the CIMP-high/MLH1 3' methylated (A), CIMP-low/MLH1 3' methylated (B), CIMP high/MLH1 3' non-methylated (C), and CIMP-low/MLH1 3' non-methylated groups (D). Overall survival rates were higher in the combined CIMP-high/MLH1 3' methylated group, compared to the other groups where the differences were not statistically significant (log-rank P = 0.0706).
Table 2.
Methylation features according to CIMP status.
Fig 2.
The relationship between MLH1 methylation and MSI.
a) Venn diagram showing the overlap of MLH1 5' methylation and 3' methylation status. The overlapping relationship between MLH1 5'—and 3' methylation status was analyzed. 10 patients were in the MLH1 5' methylated/3' methylated (A), 8 patients were in the MLH1 5' methylated/3' non-methylated (B), 1 patient was in the MLH1 5' non-methylated/3' methylated (C), and 49 patients were in the 5' non-methylated/3' non-methylated groups (D). b) The relationship between MLH1 methylation and MSI. In the MLH1 3' methylated group, >80% cases showed MSI. In contrast, in the MLH1 3' non-methylated group, almost all cases showed MSS. c) Kaplan–Meier estimate of OS in patients with MLH1 5' methylated or non-methylated gastric cancer. Kaplan–Meier survival curves were generated according to MLH1 5' methylation status. The 5-year survival rate was analyzed for the MLH1 5' group and non-methylated groups. The survival rate was slightly higher in the MLH1 5' methylated group than in the non-methylated group but the difference was not significant (log-rank P = 0.1009). d) Kaplan–Meier estimate of OS in patients with MSI or MSS gastric cancer. Kaplan–Meier survival curves were generated according to MSI status. The 5-year survival rate was analyzed for the MSI group and MSS group. The survival rate was slightly higher in the MSI group than in the non-methylated group but the difference was not significant (log-rank P = 0.1316).
Table 3.
Multivariate analysis of outcome predictors.