PRKCDBP Methylation is a Potential and Promising Candidate Biomarker for Non-small Cell Lung Cancer

Background and objectives:The occurrence and development of lung cancer are closely linked to epigenetic modification.Abnormal DNA methylation in the CpG island region of genes has been found in many cancers.Protein kinase C delta binding protein(PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies.This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer(NSCLC).Methods:We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues.Promoter activity was measured by the dual luciferase assay,with S’-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.Results:The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant(>10 cm)non-tumor tissues.Receiver operating characteristic(ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line(AUC) was 0.717.Dual luciferase experiment confirmed that the promoter region was able to promote gene expression.Meanwhile,in vitro methylation of the fragment(PRKCDBP;e) could significantly reduce the promoter activity of the fragment.Demethylation of 5’-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.Conclusion:PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.