MAPT promoter CpG island hypermethylation is associated with poor prognosis in patients with stage II colorectal cancer

Abstract

Chuntao Wang,1 Yanliang Liu,1 Wenyi Guo,1 Xu Zhu,1 Nita Ahuja,2 Tao Fu11Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China; 2Department of Surgery, Yale School of Medicine, New Haven, CT, USABackground: The methylation of microtubule-associated protein tau (MAPT) was first described in patients with Alzheimer’s disease. In this study, we aim to determine if MAPT promoter CpG island is hypermethylated and whether this signature could work as a prognostic marker for patients with stage II colorectal cancer (CRC).Methods: MAPT methylation level and CpG island methylator phenotype (CIMP) status were examined. The prognostic value of MAPT methylation was analyzed using Cox regression analysis.Results: Amongst stage II CRC patients (n=107), hypermethylation of MAPT promoter CpG island was seen in 23.4% of them. MAPT methylation was much more frequent in patients with age ≥60 compared to age <60 (P<0.001). MAPT were preferentially methylated among proximal colon tumors or CIMP high tumors (both P<0.001). Five-year overall survival (OS) rates were 57.1% and 79.4% for patients with and without MAPT hypermethylation, respectively, HR=2.33 (95% CI, 1.19–4.57; P=0.014). MAPT hypermethylation remained an important prognostic variable for OS in multivariate analysis with a HR of 2.29 (95% CI, 1.01–5.18; P=0.047).Conclusion: Our findings suggest that MAPT is frequently methylated and hypermethylation is associated with worse prognosis in patients with stage II CRC.Keywords: colorectal cancer, methylation, MAPT, prognosis

Keywords

• colorectal cancer
• methylation
• MAPT
• prognosis