Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer
Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer
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DOI：
10.1186/s12885-020-06965-4
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发表时间：
2020-05-24
期刊：
影响因子：
3.8
通讯作者：
Yoshida, Yoshio
中科院分区：
文献类型：
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作者：
Tsuyoshi, Hideaki;Orisaka, Makoto;Yoshida, Yoshio
研究背景线粒体分裂蛋白（Dynamin related protein 1，Drp 1）及其上游蛋白钙/钙调蛋白依赖性蛋白激酶I（CaMKI）在卵巢癌（Ovarian cancer，OVCA）化疗耐药中起重要作用。因此，我们研究了表达Drp 1，CaMKI和他们的磷酸化形式和他们的预后影响上皮OVCA patients.MethodsExpression免疫组化（IHC）的石蜡包埋的肿瘤样本进行分析49例上皮OVCA。染色强度和阳性染色肿瘤细胞的百分比用于计算0-12的免疫反应性评分（IRS）。结果磷酸化Drp 1（Ser 637）的高免疫反应性与高级别浆液性癌（HGSC）显著相关（P < 0. 05）。（p=0.034），术后残留肿瘤>1cm（p=0.006）和辅助化疗无应答者（p=0.007），而CaMKI的高表达与III/IV期显著相关[国际妇产科医师联合会（FIGO）]（p=0.011）和铂耐药复发（p=0.030）。ROC曲线分析显示，Drp 1、磷酸化Drp 1（Ser 637）和CaMKI可显著检测肿瘤进展，曲线下面积（AUC）分别为0.710、0.779和0.686。Kaplan-Meier生存曲线显示，Drp 1、磷酸化Drp 1（Ser 637）和CaMKI水平高的患者无进展生存期（PFS）显著较差（p=0.003，p
BackgroundThe mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin-dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients.MethodsExpression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0-12. The expression scores calculated were correlated with clinicopathological parameters and patient survival.ResultsHigh immunoreactivity of phospho-Drp1(Ser637) was significantly correlated with high-grade serous carcinoma (HGSC) (p=0.034), residual postoperative tumor of >1cm (p=0.006), and non-responders to adjuvant chemotherapy (p=0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] (p=0.011) and platinum-resistant recurrence (p=0.030). ROC curve analysis showed that Drp1, phospho-Drp1(Ser637) and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1(Ser637) and CaMKI levels had significantly poorer progression free survival (PFS) (p=0.003, p