Aberrant methylation of yes-associated protein (YAP1) as a potential biomarker in breast cancer

Abstract

Abstract Background Breast cancer (BC) represents the most prevalent malignancy among women, and it is characterized by high mortality especially in late stages. BC tumorigenesis was linked to epigenetic alterations namely methylation. Yes-associated protein (YAP1) is the leading downstream effector of the Hippo pathway. It may enhance or inhibit oncogenesis based on the tissue involved. Aim This case-control study aimed to analyze the methylation degree of promoter region of YAP1 gene in BC patients by applying methylation-specific polymerase chain reaction (MSP) analysis. Methods Genomic deoxyribonucleic acid (DNA) was isolated from 50 paired tumor and adjacent noncancerous breast tissue samples and subjected to bisulfite conversion. Methylation condition of YAP1 gene was studied by MSP and evaluated as a possible biomarker for diagnosing BC and its differentiation from corresponding normal tissues. We also correlated the aberrant methylation with clinicopathological criteria. Results Increased methylation of the YAP1 gene promoter region in BC tumor tissue was detected in 68% of the studied BC tissue samples. There was a significant change in the frequency of YAP1 methylated genotype between breast tumor tissues compared to that in adjacent non-cancerous tissue (p < 0.001). YAP1 can discriminate early from late-stage BC with a sensitivity of 96.88% and specificity of 83.33%. Conclusions Gene analysis of YAP1 using conventional MSP in tissue specimens can be considered a possible biomarker to distinguish BC from normal breast tissue as well as between early- and late-stage BC.

Keywords

• Breast cancer
• Hippo pathway
• Methylation-specific polymerase chain reaction analysis
• Yes-associated protein (YAP1)