DRP1 在卵巢上皮性癌中的预后价值。
Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer.
机构信息
Department of Obstetrics and Gynecology, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, ON, K1H 8L1, Canada.
出版信息
BMC Cancer. 2020 May 24;20(1):467. doi: 10.1186/s12885-020-06965-4.
BACKGROUND
The 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.
METHODS
Expression 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.
RESULTS
High immunoreactivity of phospho-Drp1 was significantly correlated with high-grade serous carcinoma (HGSC) (p = 0.034), residual postoperative tumor of > 1 cm (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 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 and CaMKI levels had significantly poorer progression free survival (PFS) (p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1 was significantly associated with PFS [p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039-9.561].
CONCLUSIONS
Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.
背景
线粒体裂变蛋白，DRP1（Dynamin related protein 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（OVCA）的化疗耐药中发挥着关键作用。因此，我们检测了 DRP1、CaMKI 及其磷酸化形式在上皮性 OVCA 患者中的表达及其预后意义。
方法
通过对 49 例上皮性 OVCA 患者的石蜡包埋肿瘤样本进行免疫组织化学（IHC）分析，检测 DRP1、CaMKI 及其磷酸化形式的表达。采用染色强度和阳性肿瘤细胞百分比来计算免疫反应评分（IRS），范围为 0-12。计算出的表达评分与临床病理参数和患者生存情况相关。
结果
磷酸化 DRP1 的高免疫反应性与高级别浆液性癌（HGSC）显著相关（p=0.034），与术后残余肿瘤＞1cm（p=0.006）和对辅助化疗无反应者（p=0.007）显著相关，而 CaMKI 的高表达与国际妇产科联合会（FIGO）分期 III/IV 期（p=0.011）和铂类耐药复发（p=0.030）显著相关。ROC 曲线分析显示，DRP1、磷酸化 DRP1 和 CaMKI 分别以 0.710、0.779 和 0.686 的 AUC 显著检测肿瘤进展。Kaplan-Meier 生存曲线显示，DRP1、磷酸化 DRP1 和 CaMKI 高表达的患者无进展生存期（PFS）显著较差（p=0.003、p<0.001 和 p=0.017）。多变量分析显示，磷酸化 DRP1 与 PFS 显著相关（p=0.043，HR 3.151，95%CI 1.039-9.561）。
结论
DRP1 和 CaMKI 是上皮性 OVCA 检测和预后的新的潜在候选标志物，因此应进一步研究以探索其治疗意义。
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