Fig. 1.

Global analysis identifies CBS epimutation as highly conserved in CIMP-positive GC lines. a Overlap of genes that are promoter hypermethylated (P < 0.05; FDR ≤ 0.1), and downregulated at RNA and protein levels in CIMP vs. non-CIMP GC cell line panel (log₂ FD ≤ 2, P < 0.05; FDR ≤ 0.05) (n = 14). b Percentage of CIMP-high [n = 14], CIMP-low [n = 23] and non-CIMP cell lines [n = 13] in the expanded GC cell line cohort with RPKM < 1 (gene silencing) for the 6-gene panel listed in a [left panel]; RPKM values for CBS in the expanded GC cell line cohort (*P < 0.001, Mann-Whitney test; CIMP-high vs. CIMP-low or non-CIMP) [right panel]. c Heat map representing promoter methylation β-values of CBS gene in the expanded GC cell line cohort [n = 50] (*P < 0.001, Mann-Whitney test; CIMP-high vs. CIMP-low or non-CIMP). d Heat map representing promoter methylation β-values of CBS gene [upper panel] and CBS protein levels in normal gastric, CIMP, and non-CIMP GC lines using Western blotting and densitometric normalized levels of CBS/ACTB [lower panel]. e CBS mRNA expression in GC CIMP lines can be re-instated by Azacytidine [n = 3] (P < 0.05, Student’s t test)