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Caspase recruitment domain family member 9 expression is a promising biomarker in esophageal squamous cell carcinoma

机译:Caspase招聘领域家庭成员9表达是食管鳞状细胞癌中有前途的生物标志物

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Aim Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF‐κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF‐κB activation to examine whether it can be used as a prognostic factor in ESCC. Methods We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next‐generation sequencing (NGS). Results High CARD9 expression is significantly correlated with advanced tumor depth ( P ?.001), positive lymph node metastasis ( P =?.005) and advanced stage ( P =?.001). Kaplan‐Meier method and the log‐rank test showed that overall survival (OS) and disease‐free survival (DFS) were significantly poor in the high CARD9 expression group (OS: P =?.027, DFS: P =?.005). Univariate and multivariate analysis showed that high CARD9 expression is a significant poor prognostic factor for DFS. Cell proliferation and migration were suppressed by CARD9 knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 ( MEG3 ). Conclusion High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.
机译:目的食管鳞状细胞癌(ESCC)是一种难治性消化器官癌,需要更好的治疗策略。我们最近据报道,通过抑制核因子κB(NF-κB)核易位来抑制抗糖尿病药物二甲双胍对ESCC发挥抗肿瘤作用。在本研究中,我们专注于Caspase募集结构域系列成员9(CARD9),NF-κB活化中的必需信号适配器,以检查它是否可以用作ESCC中的预后因子。方法我们研究了从93例ESCC患者接受治疗食管切除术的93例ESCC患者获得的临床样品中的CARK9表达。分析CARD9表达与临床病理特征和ESCC预后的相关性。通过敲击ESCC细胞来研究分子效果。通过下一代测序(NGS)检测这些ESCC细胞中综合的RNA表达变化。结果高CAMP9表达与晚期肿瘤深度(P <α.001),阳性淋巴结转移(P = 005)和高级阶段(P =〜001)明显相关。 Kaplan-Meier方法和日志秩检验显示,高CARK9表达组(OS:P =β.027,DFS:P =Δ.005 )。单变量和多变量分析表明,高卡9表达是DFS的显着差的预后因素。 CARD9敲低抑制细胞增殖和迁移。检测到NGS改变了一些RNA的表达,包括母体表达3(MEG3)。结论高卡9表达明显与预后差有关。因此,CARD9表达可以是ESCC中的前瞻性预后生物标志物。

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