The Identification and Validation of EphA7 Hypermethylation, a Novel Biomarker, in Cervical Cancer

Abstract Background Aberrant methylation of EphA7 has been reported in the process of carcinogenesis,but not including cervical cancer.Therefore,an integration study was performed to explore the association between EphA7 hypermethylation and cervical cancer and validate the potential value of EphA7 hypermethylation in the diagnosis of cervical cancer. Results Here, we performed an integration study to identify and validate the association between EphA7 methylation and cervical cancer. First, data on EphA7 methylation and expression in cervical cancer were extracted and analyzed via bioinformatics tools. The results showed that EphA7 promoter methylation levels were significantly increased in cervical cancer compared to normal tissues (P<0.001) and negatively correlated with EphA7 expression. Subsequently, these prediction results were confirmed in cell lines; moreover, CRISPR-based methylation perturbation tools (dCas9-Tet1/DNMT3a) were constructed to further demonstrate that DNA methylation participates in the regulation of EphA7 expression directly. Ultimately, the clinical value of EphA7 methylation in cervical cancer was validated in cervical tissues and Thinprep cytologic test (TCT) samples by methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP), respectively. Consistently, the methylation level and the positive rate of EphA7 gradually increased with severity from normal to cancer stages in TCT samples (P<0.01). Conclusion Above all, EphA7 presents hypermethylation in the cervical cancer,which is a potential biomarker in the diagnosis of cervical cancer.