Department of Obstetrics and Gynaecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Institute of Biopharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Aging (Albany NY). 2022 May 4;14(9):3874-3886. doi: 10.18632/aging.204050.
Early diagnosis of ovarian cancer and the discovery of prognostic markers can significantly improve survival and reduce mortality. OPA3 protein exists in a structure called mitochondria, which is the energy production center of cells, but its molecular and biological functions in ovarian cancer are still unclear. Here, the expression of OPA3 mRNA in ovarian cancer was estimated using TCGA, Oncomine, TIMER databases. We found that functional OPA3 activation caused by mutations and profound deletions predicted poor prognosis in OV patients. OPA3 was highly expressed in both OV tissues and cells compared to normal ovarian tissues/cells. High OPA3 expression is associated with poorer overall survival (OS). The association between OPA3 and immune infiltration of ovarian cancer was assessed by TIMER and CIBERSORT algorithms. OPA3 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of OV cell lines revealed that OPA3 inactivation was associated with increased sensitivity to PFI-1, and WZ4003. Therefore, we investigated the clinical application of OPA3 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of ovarian cancer.
早期诊断卵巢癌和发现预后标志物可以显著提高生存率并降低死亡率。OPA3 蛋白存在于一种称为线粒体的结构中，线粒体是细胞的能量产生中心，但它在卵巢癌中的分子和生物学功能尚不清楚。在这里，使用 TCGA、Oncomine、TIMER 数据库估计了卵巢癌中 OPA3 mRNA 的表达。我们发现突变和深刻缺失引起的功能性 OPA3 激活预测 OV 患者预后不良。与正常卵巢组织/细胞相比，OPA3 在 OV 组织和细胞中均高度表达。高 OPA3 表达与总生存期（OS）较差相关。通过 TIMER 和 CIBERSORT 算法评估了 OPA3 与卵巢癌免疫浸润的相关性。OPA3 与各种免疫标志物集呈强相关性。最重要的是，OV 细胞系的遗传药理学分析表明，OPA3 失活与对 PFI-1 和 WZ4003 的敏感性增加有关。因此，我们研究了 OPA3 的临床应用，为卵巢癌的敏感诊断、预后和靶向治疗提供了依据。
