DNA hypermethylation of MAL gene may act as an independent predictor of favorable prognosis in patients with colorectal cancer

Xinyan Liu, Haoran Bi, Anqi Ge, Tingting Xia, Jinming Fu, Yupeng Liu, Hongru Sun, Dapeng Li, Yashuang Zhao


Background: Aberrant DNA methylation could be used as biomarkers for colorectal cancer (CRC) detection and assessment of prognosis. The aim of our study was to investigate the potential possibility of MAL methylation as a prognostic biomarker for postoperative CRC patients.
Methods: We followed up 298 sporadic postoperative CRC patients and detected MAL methylation in tumor tissues and adjacent non-tumor tissues by methylation-sensitive high resolution melting (MS-HRM) analysis. Univariate, multivariate Cox regressions were performed to evaluate the potential possibility of MAL methylation as a predictor of prognosis. Propensity score (PS) analysis was used to control confounders.
Results: The MAL methylation level in adjacent non-tumor tissues was significantly lower than that in tumor tissues (P<0.001). The MAL methylation had no significant correlation with clinicopathologic characteristics. MAL hypermethylation was detected in 63.4% (189/298) tumor tissues. The overall 5-year survival rates in hypermethylation and hypomethylation group were 70.78% and 55.69% (P=0.007). MAL hypermethylation was significantly associated with a favorable clinical outcome, the hazard ratio (HR) were 0.650 [95% confidence interval (CI): 0.454–0.929, P=0.018], 0.613 (95% CI: 0.422–0.889, P=0.010) and 0.692 (95% CI: 0.481–0.996, P=0.047) in univariate, multivariate Cox and PS method, respectively. The subgroup analysis showed that MAL hypermethylation in CRC patients with lower diagnosis age (<60) and colon cancer had a lower risk of death than MAL hypomethylation patients.
Conclusions: MAL was frequently hypermethylated in CRC tumor tissues. MAL hypermethylation might act as an independent prognostic predictor of survival advantage in postoperative patients with CRC.