Balakrishnan Karthik, Chen Yuanhong, Dong Jixin
Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cancers (Basel). 2024 May 5;16(9):1781. doi: 10.3390/cancers16091781.
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 significant -values ( < 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。因此，与Hippo信号通路相关的特征是从分子特征数据库（MSigDB）中获得的，并用于进一步分析。采用基于Z评分的通路激活评分方法来研究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，本研究结果表明，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）基因的结果可以通过更高的特异性和敏感性预测浆液性亚型肿瘤，曲线下的显著面积值也进一步证实了这些信号失调。此外，在cBioPortal数据库中对高级别浆液性卵巢腺癌的图谱进行了进一步的这些基因集的突变分析研究。OncoPrint结果显示，在浆液性卵巢肿瘤的三级和三期或四期，这些Hippo信号通路基因高度扩增。此外，依赖性图谱（DepMap）图的结果也清楚地表明，这些基因在卵巢癌细胞系中显著扩增。最后，总生存（OS）曲线图谱研究还显示，这些基因表达显示出与浆液性亚型卵巢癌患者高表达状态相关的不良生存模式，具有显著的P值（<0.05）。因此，目前的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。
