干扰素诱导蛋白27和动力蛋白3表达与上皮性卵巢癌血管生成及铂耐药复发的关系研究

Relationship between expression of interferon-induced protein 27 and dynamin 3 with angiogenesis and platinum-resistant recurrence in epithelial ovarian cancer

  • 摘要:
    目的 探讨干扰素诱导蛋白27(IFI27)和动力蛋白3(DNM3)表达与上皮性卵巢癌(EOC)血管生成及铂耐药复发的关系。
    方法 采用前瞻性队列研究设计,纳入129例拟行手术联合铂类药物化疗的EOC患者作为研究对象。收集患者的癌组织及癌旁组织,采用实时荧光定量聚合酶链式反应(qRT-PCR)检测组织样本中IFI27 mRNA、DNM3 mRNA表达水平; 采用免疫组织化学法(IHC)检测血管生成标志物微血管密度(MVD)、血管内皮生长因子(VEGF)表达。患者术后接受标准铂类药物化疗方案,定期随访复发情况并分为铂耐药组和铂敏感组,分析IFI27、DNM3表达与铂耐药复发的关联。
    结果 129例患者均完成手术联合化疗,将49例化疗耐药复发患者归为铂耐药组,其余80例患者归为铂敏感组, 2组患者分化程度差异有统计学意义(P=0.001)。癌组织中IFI27 mRNA表达水平高于癌旁组织, DNM3 mRNA表达水平低于癌旁组织, MVD、VEGF表达水平高于癌旁组织,差异有统计学意义(P < 0.001); 铂耐药组IFI27 mRNA表达水平高于铂敏感组, DNM3 mRNA表达水平低于铂敏感组, MVD、VEGF表达水平高于铂敏感组,差异有统计学意义(P < 0.05或P < 0.001)。Pearson相关分析显示, EOC患者VEGF、MVD表达分别与IFI27表达呈正相关(r=0.643、0.765, P < 0.05), 分别与DNM3表达呈负相关(r=-0.573、-0.632, P < 0.05)。低分化程度、IFI27高表达是EOC患者铂耐药复发的独立危险因素(P < 0.05), DNM3高表达是独立保护因素(P < 0.05)。受试者工作特征曲线显示, IFI27、DNM3联合预测EOC患者铂耐药复发的曲线下面积(AUC)为0.863, 大于二者单独预测的AUC(0.815、0.704)。
    结论 IFI27高表达和DNM3低表达与EOC血管生成及铂耐药复发显著相关,二者联合检测对EOC患者1年内铂耐药复发具有较高的预测效能。

     

    Abstract:
    Objective To investigate the relationships of the expression of interferon-induced protein 27 (IFI27) and dynamin 3 (DNM3) with angiogenesis and platinum-resistant recurrence in epithelial ovarian cancer (EOC).
    Methods A prospective cohort study design was adopted, and 129 EOC patients scheduled for surgery combined with platinum-based chemotherapy were enrolled as the study subjects. Cancerous tissues and adjacent non-cancerous tissues were collected from the patients. The expression levels of IFI27 mRNA and DNM3 mRNA in the tissue samples were detected using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The expressions of angiogenesis markers, microvascular density (MVD) and vascular endothelial growth factor (VEGF), were detected by immunohistochemistry (IHC). After surgery, the patients received standard platinum-based chemotherapy regimen. They were regularly followed up for recurrence and divided into platinum-resistant group and platinum-sensitive group. The associations of the expressions of IFI27 and DNM3 with platinum-resistant recurrence were analyzed.
    Results All 129 patients completed surgery combined with chemotherapy. Forty-nine patients with chemotherapy-resistant recurrence were included in platinum-resistant group, and the remaining 80 patients were included in platinum-sensitive group. There was a significant difference in the degree of differentiation between the two groups (P=0.001). The expression level of IFI27 mRNA in cancerous tissues was higher than that in adjacent non-cancerous tissues, while the expression level of DNM3 mRNA was lower than that in adjacent non-cancerous tissues. The expression levels of MVD and VEGF were higher than those in adjacent non-cancerous tissues, with statistically significant differences (P < 0.001). In the platinum-resistant group, the expression level of IFI27 mRNA was higher than that in the platinum-sensitive group, the expression level of DNM3 mRNA was lower than that in the platinum-sensitive group, and the expression levels of MVD and VEGF were higher than those in the platinum-sensitive group, with statistically significant differences (P < 0.05 or P < 0.001). Pearson correlation analysis showed that the expressions of VEGF and MVD in EOC patients were positively correlated with the expression of IFI27 (r=0.643, 0.765, P < 0.05), respectively, and negatively correlated with the expression of DNM3 (r=-0.573, -0.632, P < 0.05), respectively. Low degree of differentiation and high expression of IFI27 were independent risk factors for platinum-resistant recurrence in EOC patients (P < 0.05), while high expression of DNM3 was an independent protective factor (P < 0.05). The receiver operating characteristic curve showed that the area under the curve (AUC) for the combined prediction of platinum-resistant recurrence in EOC patients by IFI27 and DNM3 was 0.863, which was greater than the AUCs for their individual indicators (0.815, 0.704).
    Conclusion High expression of IFI27 and low expression of DNM3 are significantly associated with angiogenesis and platinum-resistant recurrence in EOC. Their combined detection has a high predictive efficacy for platinum-resistant recurrence in EOC patients within one year.

     

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