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. 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. 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. 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%. 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.

中文翻译：

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yes 相关蛋白 (YAP1) 的异常甲基化作为乳腺癌的潜在生物标志物

乳腺癌（BC）是女性中最普遍的恶性肿瘤，其特点是死亡率高，尤其是晚期。BC 肿瘤发生与表观遗传改变即甲基化有关。Yes 相关蛋白 (YAP1) 是 Hippo 通路的主要下游效应子。根据所涉及的组织，它可能会增强或抑制肿瘤发生。本病例对照研究旨在通过应用甲基化特异性聚合酶链反应 (MSP) 分析来分析 BC 患者 YAP1 基因启动子区的甲基化程度。基因组脱氧核糖核酸 (DNA) 从 50 对肿瘤和邻近的非癌乳腺组织样本中分离出来，并进行亚硫酸氢盐转化。通过 MSP 研究 YAP1 基因的甲基化状况，并评估其作为诊断 BC 及其与相应正常组织分化的可能生物标志物。我们还将异常甲基化与临床病理学标准相关联。在 68% 的研究 BC 组织样本中检测到 BC 肿瘤组织中 YAP1 基因启动子区域的甲基化增加。与邻近的非癌组织相比，乳腺肿瘤组织之间 YAP1 甲基化基因型的频率存在显着变化（p < 0.001）。YAP1 可以区分早期和晚期 BC，灵敏度为 96.88%，特异性为 83.33%。在组织标本中使用常规 MSP 对 YAP1 进行基因分析可以被认为是区分 BC 与正常乳腺组织以及早期和晚期 BC 的可能生物标志物。