YAP1在激素受体阳性、人表皮生长因子受体2阴性乳腺癌中的表达：21基因复发评分分析及公共数据集验证
YAP1 Expression in HR+HER2- Breast Cancer: 21-Gene Recurrence Score Analysis and Public Dataset Validation.
作者信息
Park Inho, Lee Yangkyu, Kim Jee Hung, Bae Soong June, Ahn Sung Gwe, Jeong Joon, Cha Yoon Jin
机构信息
Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.
Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.
出版信息
Cancers (Basel). 2023 Oct 18;15(20):5034. doi: 10.3390/cancers15205034.
BACKGROUND
YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2-) breast cancer.
METHODS
We retrospectively analyzed 401 HR+HER2- breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014-April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes.
RESULTS
YAP1 expression negatively correlated with ODX RS (OR 0.373, = 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets ( < 0.0001 OS in METABRIC, = 0.00085 RFS in METABRIC, = 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed.
CONCLUSION
YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2- breast cancer patients.
背景
YAP1是多种癌症中的一种致癌基因，是Hippo信号通路的下游转录因子。本研究聚焦于其与激素受体阳性、人表皮生长因子受体2阴性（HR+HER2-）乳腺癌患者的Oncotype Dx（ODX）检测风险评分（RS）之间的关系。
方法
我们回顾性分析了401例来自江南Severance医院接受ODX检测（2014年5月至2020年4月）的HR+HER2-乳腺癌患者。通过免疫组化染色评估YAP1的核定位，并分析其与包括RS在内的临床病理参数的临床相关性。公开数据集TCGA-BRCA和METABRIC验证了临床结果。
结果
YAP1表达与ODX RS呈负相关（OR 0.373，P = 0.002）。YAP1 mRNA水平升高对应更好的临床结果，特别是在雌激素受体阳性患者中，在METABRIC和TCGA-BRCA数据集中有显著结果（METABRIC中总生存期P < 0.0001，METABRIC中无进展生存期P = 0.00085，TCGA-BRCA中无病生存期P = 0.040）。在ESR1 mRNA表达不同且YAP1表达明显的亚组中，始终观察到更好的生存结果。
结论
YAP1可能是HR+HER2-乳腺癌患者中有价值的预后标志物和潜在治疗靶点。
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