Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer

Clinical Epigenetics

Yichao Wang¹  Dong Dong²  Aimin Zhang²  Jie Shao²  Yueguo Li²  Yunli Zhou²  Runshi Zhang³ 

[1] Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou University Hospital), No.999 Donghai Road, Jiaojiang District, 318000, Taizhou, Zhejiang Province, People’s Republic of China;Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, 300060, Tianjin, People’s Republic of China;Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, 300060, Tianjin, People’s Republic of China;Department of Clinical Laboratory, Xi’an No. 1 Hospital, 710002, Xi’an, Shaanxi, People’s Republic of China;

关键词: UNC5 receptors;    Methylation;    Expression;    Colorectal cancer;    Prognosis;   

DOI  :  10.1186/s13148-021-01211-5

来源: Springer

【 摘 要 】

BackgroundDeregulated methylation of tumor suppressor genes is a hallmark event in colorectal cancer (CRC) carcinogenesis. UNC5 receptors, down-regulated in various human malignancies due to epigenetic alterations, have been proposed as putative tumor suppressor genes. In this study, we focused on the methylation-mediated inhibition of UNC5 receptors and the associated clinical significance in CRC.MethodsMethylation and expression analysis was performed in TCGA datasets. And the results were confirmed in vitro in CRC cell lines treated with 5-aza-deoxycytidine. Then, the expression and epigenetic alterations of UNC5 receptors were evaluated in clinical specimens. Moreover, the diagnostic and prognostic values of the methylation alterations were also analyzed.ResultsMethylation-mediated repression was observed in UNC5C and UNC5D, but not in UNC5A and UNC5B, which was confirmed in CRC cell lines. Except for UNC5B, significantly elevated methylation was observed in UNC5A, UNC5C, and UNC5D in CRC. The discrimination efficiency of the three receptors was comparable with that of SEPT9. Kaplan–Meier curve survival analysis showed that hypermethylation of UNC5A, UNC5C and UNC5D was associated with poor progression-free and overall survival. Moreover, methylation levels of UNC5C and UNC5D were independent predictors of CRC progression-free (P = 0.001, P = 0.003, respectively) and overall survival (P = 0.008, P = 0.004, respectively).ConclusionsHypermethylation of UNC5C and UNC5D mediates the repression and has promising diagnostic and prognostic values in CRC.

【 授权许可】

CC BY