title: Promoter hypermethylation of miR-34a contributes to the risk, progression, metastasis and poor survival of laryngeal squamous cell carcinoma.
abstract: MiR-34a is a direct transcriptional target of p53, which induces cell cycle arrest, senescence, and apoptosis. Recently, we and others identified abnormal expression of miR-34a in laryngeal squamous cell carcinoma (LSCC). The aim of our present study was to investigate the contribution of miR-34a promoter methylation to LSCC. Bisulfite pyrosequencing technology was applied to measure DNA methylation levels of six CpG sites in the miR-34a promoter from 104 LSCC tumor tissues and their corresponding adjacent tissues. Our results showed that the methylation levels of the miR-34a promoter were significantly higher in cancer tissues compared with the adjacent tissues (adjusted P=5.05E-10). A breakdown analysis for cigarette smoking behavior indicated a significantly elevated tendency of miR-34a methylation level in LSCC patients with smoking behavior but not in LSCC patients without smoking behavior (Smoking: Tumor vs Normal, adjusted P=3.12E-9; Non-smoking: Tumor vs Normal, adjusted P=0.073). In addition, miR-34a promoter methylation frequency remarkably increased in the advanced stage patients (adjusted P=0.003) and advanced T classified tumors (adjusted P=0.015). Moreover, significant association of miR-34a promoter hypermethylation with LSCC lymph metastasis was observed (adjusted P=0.002). Meanwhile, Kaplan-Meier survival curves results showed that high methylation of miR-34a promoter were associated with poor overall survival (log-rank test, P=0.023). Our study revealed that miR-34a promoter hypermethylation was a risk factor for LSCC, played a critical role in the disease progression and metastasis, and could serve as a poor prognostic factor for LSCC.
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China. Electronic address: szs7216@163.com.
authors.forename: Zhisen
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Chongchang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Jinyun
authors.initials: J
authors.lastname: Li
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Lihuili Hospital of Ningbo University, Ningbo 315040, China; The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Tianlian
authors.initials: T
authors.lastname: Bao
authors.affiliation: The Medical School of Ningbo University, Ningbo 315211, China. Electronic address: duanshiwei@nbu.edu.cn.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: DNA methylation; LSCC; Prognosis; Promoter; miR-34a