Among women, ovarian cancer ranks as the fifth most common cause of cancer-related deaths. This study examined the impact of Hippo signaling pathway on ovarian carcinogenesis. Therefore, the signatures related to Hippo signaling pathway were derived from the molecular signatures database (MSigDB) and were used for further analysis. The Z score-based pathway activation scoring method was employed to investigate the expression patterns of these signatures in the mRNA expression profiles of ovarian cancer cohorts. Compared to other subtype tumors, the results of this study show that the Hippo signaling pathway signatures are dysregulated prominently in serous subtype-specific ovarian carcinogenesis. A receiver operating characteristic (ROC) curve-based results of the Hippo gene set, yes-associated protein 1 (YAP1), and mammalian sterile 20-like kinases 1 (MST1) genes can predict the serous subtype tumors by higher specificity and sensitivity with significant areas under the curve values also further reconfirmed these signaling dysregulations. Moreover, these gene sets were studied further for mutation analysis in the profile of high-grade serous ovarian adenocarcinoma in the cBioPortal database. The OncoPrint results reveal that these Hippo signaling pathway genes are amplified highly during the grade three and stage third or fourth of serous type ovarian tumors. In addition, the results of the Dependency Map (DepMap) plot also clearly show that these genes are amplified significantly across the ovarian cancer cell lines. Finally, overall survival (OS) curve plot investigations also revealed that these gene expressions show poor survival patterns linked to highly expressed conditions in serous subtypes of ovarian cancer patients with significantp-values (p< 0.05). Thus, the current finding would help to develop the targeted therapies treatment for serous subtype ovarian carcinogenesis.
在女性中，卵巢癌是癌症相关死亡的第五大常见原因。本研究探讨了Hippo信号通路对卵巢癌发生的影响。为此，从分子特征数据库（MSigDB）中提取了与Hippo信号通路相关的特征，并用于进一步分析。采用基于Z分数的通路激活评分方法，研究了这些特征在卵巢癌队列mRNA表达谱中的表达模式。与其他亚型肿瘤相比，本研究结果显示，Hippo信号通路特征在浆液性亚型特异性卵巢癌发生中显著失调。基于受试者工作特征（ROC）曲线的Hippo基因集、Yes相关蛋白1（YAP1）和哺乳动物不育20样激酶1（MST1）基因的结果，能够以较高的特异性和敏感性预测浆液性亚型肿瘤，且曲线下面积值显著，进一步证实了这些信号通路的失调。此外，在cBioPortal数据库中对这些基因集进行了高级别浆液性卵巢腺癌的突变分析。OncoPrint结果显示，这些Hippo信号通路基因在三级及三期或四期浆液性卵巢肿瘤中高度扩增。同时，依赖性图谱（DepMap）的结果也清楚显示，这些基因在卵巢癌细胞系中显著扩增。最后，总生存期（OS）曲线图研究还揭示，这些基因的表达在浆液性亚型卵巢癌患者高表达状态下显示出较差的生存模式，且具有显著的p值（p < 0.05）。因此，本发现将有助于开发针对浆液性亚型卵巢癌发生的靶向治疗。
肿瘤(癌症)患者之家