Sekino Nobufumi, Kano Masayuki, Sakata Haruhito, Murakami Kentaro, Toyozumi Takeshi, Matsumoto Yasunori, Ryuzaki Takahiro, Ikeda Junichiro, Ota Masayuki, Matsubara Hisahiro
Department of Frontier Surgery Graduate School of Medicine Chiba University Chiba Japan.
Department of Diagnostic Pathology Graduate School of Medicine Chiba University Chiba Japan.
Ann Gastroenterol Surg. 2019 Dec 22;4(2):135-141. doi: 10.1002/ags3.12305. eCollection 2020 Mar.
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.
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).
High CARD9 expression is significantly correlated with advanced tumor depth ( < .001), positive lymph node metastasis ( = .005) and advanced stage ( = .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: = .027, DFS: = .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 knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 ().
High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.
食管鳞状细胞癌（ESCC）是一种难治性消化器官癌症，需要更好的治疗策略。我们最近报道，抗糖尿病药物二甲双胍通过抑制核因子κB（NF-κB）核转位对ESCC发挥抗肿瘤作用。在本研究中，我们聚焦于半胱天冬酶募集结构域家族成员9（CARD9），它是NF-κB激活过程中的一种重要信号衔接蛋白，以研究其是否可作为ESCC的预后因素。
我们采用免疫组织化学方法研究了93例行根治性食管切除术的ESCC患者临床样本中的CARD9表达情况。分析CARD9表达与临床病理特征及ESCC预后的相关性。通过敲低ESCC细胞来研究其分子效应。采用下一代测序（NGS）检测这些ESCC细胞中全面的RNA表达变化。
CARD9高表达与肿瘤深度增加（<0.001）、阳性淋巴结转移（=0.005）和晚期（=0.001）显著相关。Kaplan-Meier法和对数秩检验显示，CARD9高表达组的总生存期（OS）和无病生存期（DFS）显著较差（OS：=0.027，DFS：=0.005）。单因素和多因素分析显示，CARD9高表达是DFS的一个显著不良预后因素。敲低可抑制细胞增殖和迁移。NGS检测到包括母源表达基因3（）在内的一些RNA的表达发生了改变。
CARD9高表达与不良预后显著相关。因此，CARD9表达可能是ESCC中一种有前景的预后生物标志物。
