Overexpression of TRIM44 is related to invasive potential and malignant outcomes in esophageal squamous cell carcinoma
Overexpression of TRIM44 is related to invasive potential and malignant outcomes in esophageal squamous cell carcinoma
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DOI：
10.1177/1010428317700409
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发表时间：
2017-06-15
期刊：
影响因子：
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通讯作者：
Otsuji, Eigo
中科院分区：
文献类型：
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作者：
Kawaguchi, Tsutomu;Komatsu, Shuhei;Otsuji, Eigo
最近的研究表明，含有三个基序的蛋白家族中的一些成员在癌症发生中起着重要的调节作用。在这项研究中，我们研究了含三方基序的蛋白44是否通过其在食管鳞状细胞癌中的过表达而发挥促癌基因的作用。我们分析了食管鳞癌细胞系以评估恶性潜能，并分析了68例原发肿瘤以评估三方基序含蛋白44蛋白在食管鳞癌患者中的临床意义。含三方模体蛋白44蛋白在食管鳞癌细胞系(8/14株，57%)和原发癌组织(39/68例，57%)中均有表达。使用几种特定的小干扰RNA抑制食管鳞状细胞癌细胞中含三方基序的蛋白44的表达可抑制细胞的迁移和侵袭，但不能抑制细胞的增殖。免疫组织化学分析显示，肿瘤浸润区内含三方基序蛋白44蛋白的过度表达与淋巴结转移状态有关(p=0.049)，含三方基序蛋白44高表达肿瘤患者的总体生存率明显低于无表达肿瘤患者(p=0.029)。此外，多因素COX回归模型显示，含三方基序的蛋白44蛋白过度表达是预后较差的独立因素(风险比=2.815；p=0.041)，也是影响淋巴转移的独立因素(风险比=2.735；p=0.037)。这些结果表明，含三方基序的蛋白44蛋白可能通过其过表达在肿瘤侵袭中发挥重要作用，并强调其作为食管鳞癌的预测指标和潜在的治疗靶点的作用。
Recent studies have shown that some members of the tripartite motif-containing protein family function as important regulators for carcinogenesis. In this study, we investigated whether tripartite motif-containing protein 44 acts as a cancer-promoting gene through its overexpression in esophageal squamous cell carcinoma. We analyzed esophageal squamous cell carcinoma cell lines to evaluate malignant potential and also analyzed 68 primary tumors to evaluate clinical relevance of tripartite motif-containing protein 44 protein in esophageal squamous cell carcinoma patients. Expression of the tripartite motif-containing protein 44 protein was detected in esophageal squamous cell carcinoma cell lines (8/14 cell lines; 57%) and primary tumor samples of esophageal squamous cell carcinoma (39/68 cases; 57%). Knockdown of tripartite motif-containing protein 44 expression in esophageal squamous cell carcinoma cells using several specific small interfering RNAs inhibited cell migration and invasion, but not cell proliferation. Immunohistochemical analysis demonstrated that the overexpression of the tripartite motif-containing protein 44 protein in the tumor infiltrated region was associated with the status of lymph node metastasis (p = 0.049), and the overall survival rates were significantly worse among patients with tripartite motif-containing protein 44-overexpressing tumors than those with non-expressing tumors (p = 0.029). Moreover, multivariate Cox regression model identified that overexpression of the tripartite motif-containing protein 44 protein was an independent worse prognostic factor (hazard ratio = 2.815; p = 0.041), as well as lymphatic invasion (hazard ratio = 2.735; p = 0.037). These results suggest that tripartite motif-containing protein 44 protein could play a crucial role in tumor invasion through its overexpression and highlight its usefulness as a predictor and potential therapeutic target in esophageal squamous cell carcinoma.