Venkatasubramanian Gomathi, Kelkar Devaki A, Mandal Susmita, Jolly Mohit Kumar, Kulkarni Madhura
Centre for Translational Cancer Research: A Joint Initiative of Prashanti Cancer Care Mission and Indian Institute of Science Education and Research, Pune 411016, India.
Prashanti Cancer Care Mission, 1-2 Kapil Vastu, Senapati Bapat Road, Pune 411016, India.
J Clin Med. 2022 Mar 31;11(7):1947. doi: 10.3390/jcm11071947.
Breast cancers are treated according to the ER/PR or HER2 expression and show better survival outcomes with targeted therapy. Triple-negative breast cancers (TNBCs) with a lack of expression of ER/PR and HER2 are treated with systemic therapy with unpredictable responses and outcomes. It is essential to investigate novel markers to identify targeted therapies for TNBC. One such marker is YAP1, a transcription co-activator protein that shows association with poor prognosis of breast cancer. YAP1 transcriptionally regulates the expression of genes that drive the oncogenic phenotypes. Here, we assess a potential YAP target gene signature to predict a progressive subset of breast tumors from METABRIC and TCGA datasets. YAP1 target genes were shortlisted based on expression correlation and concordance with YAP1 expression and significant association with survival outcomes of patients. Hierarchical clustering was performed for the shortlisted genes. The utility of the clustered genes was assessed by survival analysis to identify a recurring subset. Expression of the shortlisted target genes showed significant association with survival outcomes of HER2-positive and TNBC subset in both datasets. The shortlisted genes were verified using an independent dataset. Further validation using IHC can prove the utility of this potential prognostic signature to identify a recurrent subset of HER2-positive and TNBC subtypes.
乳腺癌根据雌激素受体（ER）/孕激素受体（PR）或人表皮生长因子受体2（HER2）的表达情况进行治疗，靶向治疗可带来更好的生存结果。缺乏ER/PR和HER2表达的三阴性乳腺癌（TNBC）采用全身治疗，但其反应和结果难以预测。研究用于识别TNBC靶向治疗的新型标志物至关重要。YAP1就是这样一种标志物，它是一种转录共激活蛋白，与乳腺癌的不良预后相关。YAP1通过转录调控驱动致癌表型的基因表达。在此，我们评估一种潜在的YAP靶基因特征，以从METABRIC和TCGA数据集中预测乳腺肿瘤的进展亚组。基于表达相关性、与YAP1表达的一致性以及与患者生存结果的显著关联，筛选出YAP1靶基因。对筛选出的基因进行层次聚类。通过生存分析评估聚类基因的效用，以识别一个反复出现的亚组。在两个数据集中，筛选出的靶基因表达均与HER2阳性和TNBC亚组的生存结果显著相关。使用独立数据集对筛选出的基因进行了验证。通过免疫组化进一步验证可证明这种潜在的预后特征在识别HER2阳性和TNBC亚型的复发亚组方面的效用。
