Aberrant Methylation of the VIM Promoter in Uterine Cervical Squamous Cell Carcinoma

Abstract

Objectives: To identify prognosis-associated methylation markers of uterine cervical squamous cell carcinoma (SCC) and to verify potential clinical correlations. Methods: A genome-wide methylation array was performed using tissue samples of stage Ib1 (n = 9) and IIa (n = 5) tumors. Methylation levels were quantitatively evaluated by pyrosequencing for 54 tissue samples from SCC patients and 22 samples from normal controls. Clinicopathologic findings were obtained from medical records. Correlation or t test statistics were used to analyze the relationships between methylation levels and clinical features. Survival data were estimated using the Kaplan-Meier method and compared to the log-rank test. Results: The methylation array identified 32 genes with distinct differences (p < 0.01) between stage Ib1 and IIa disease, and VIM was selected for further evaluation. Pyrosequencing analysis revealed that 40.7% of carcinoma samples had a higher methylation level in the VIM gene compared to the normal controls. VIM methylation status, low FIGO stage, and lack of parametrial involvement were significantly associated with longer disease-free survival (p = 0.036, p = 0.028, and p = 0.001, respectively). Conclusions: We profiled 32 genes that might be associated with prognosis in cervical cancer. We further revealed that the VIM gene is frequently methylated in cervical SCC and that its methylation might predict a favorable prognosis.