Hypomethylation may drive CLPB overexpression which predicts poor survival outcomes in breast cancer

Background: CLPB has oncogenic properties in leukemia and melanoma. We aimed to reveal the subtype-specific expression of the CLPB gene in breast cancer, its effect on survival, and genetic/epigenetic alterations that might regulate the expression. Methods: Expression levels and prognostic signatures of CLPB gene in breast cancer patients were evaluated by using in-silico tools. RT-PCR and Q-RT-PCR methods are used to examine CLPB expression in cell lines. Genetic alterations of CLPB were revealed by employing Sanger Cosmic database. Combined bisulfite restriction analysis and UALCAN tool were used to examine the methylation status of the CLPB promoter in cell lines and samples, respectively. Results: CLPB expression is significantly higher in all breast cancer subtypes compared to normals, and it is associated with worse survival values. Genetic alterations of CLPB are rare. Cell lines express CLPB gene at moderate to high levels. The promoter region of CLPB is hypomethylated in samples and cell lines. Conclusions: We suggest CLPB gene as a therapeutic target and biomarker candidate in breast cancer. The rarity of genetic alterations suggests that they do not affect CLPB regulation, but promoter hypomethylation would be one of the reasons for its high expression in breast cancer.