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Expression and prognostic significance of NKD2 in ovarian cancer.

NKD2在卵巢癌中的表达及预后意义.

  • 影响因子:2.04
  • DOI:10.1093/jjco/hyaa244
  • 作者列表:"Wei W","Zheng L","Gao Y","He M","Yang F
  • 发表时间:2021-03-03
Abstract

PURPOSE:Naked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown. PATIENTS AND METHODS:Gene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis. RESULTS:NKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P < 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58-5.85, P < 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61-5.27, P < 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80-7.21, P < 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration. CONCLUSION:NKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.

摘要

目的: Naked2 (NKD2) 是Wnt信号通路的负调控因子,与转化生长因子分泌有关。NKD2在卵巢癌中的作用尚不清楚。 患者和方法: 通过RNA测序测量并比较9例患者的基因表达谱。采用逆转录聚合酶链反应和western blot检测NKD2在卵巢癌中的表达。对79名患者的组织载玻片进行染色并对NKD2表达进行评分。体外实验探讨NKD2在卵巢癌中的作用。通过生存分析评估NKD2的预后作用。 结果: NKD2通过mRNA和蛋白表达在存活较好的患者中上调。根据免疫组化评分将患者分为NKD2-high组 (n = 30) 和NKD2-low组 (n = 49)。高NKD2与较低的复发率 (P = 0.002) 和较高的铂敏感复发百分比 (P = 0.006) 相关。NKD2-high例患者的中位无进展生存期显著长于NKD2-low例患者 (49.1 vs.14.1个月,P <0.001)。因此,两组之间的总生存时间存在显著差异 (风险比: 3.04; 95% 置信区间: 1.58-5.85,P <0.001)。多变量回归提示NKD2是无进展生存期 (风险比: 2.91; 95% 置信区间: 1.61-5.27,P <0.001) 和总生存期 (风险比: 3.6; 95% 置信区间: 1.80-7.21,P <0.001) 的独立预后因素。体外研究进一步证明NKD2抑制卵巢癌细胞增殖、集落形成和细胞迁移。 结论: NKD2是一种新的卵巢癌预后标志物,可抑制卵巢癌的进展。

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