Aberrantly Methylated and Expressed Genes as Prognostic Epigenetic Biomarkers for Colon Cancer.

This study aimed to identify prognostic epigenetic biomarkers for colon cancer (CC). Methylation and mRNA expression in CC samples with clinical characteristics that corresponded to those in The Cancer Genome Atlas were analyzed. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were screened between matched tumor and nontumor tissues. Among the 415 DEGs and DMGs that significantly correlated between cytosine-phosphate-guanine (CpG) methylation and gene expression, unc-5 netrin receptor C (UNC5C), solute carrier family 35 member F (SLC35F)1, Ly6/Neurotoxin (LYNX)1, stathmin (STMN)2, slit guidance ligand (SLIT)3, cell adhesion molecule L1 like (CHL1), CAP-Gly domain containing linker protein family member 4 (CLIP4), transmembrane protein (TMEM) 255A, granzyme B (GZMB), and brain expressed X-Linked (BEX)1 were promising epigenetic biomarkers. Prediction was more accurate when models were based on the expression and/or methylation of GZMB rather than clinical stage. Comparisons of tissues with high or low GZMB expression significantly associated the DEGs with natural killer-mediated cytotoxicity, cytokine-cytokine receptor interactions, and chemokine signaling pathways. From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.