Kawaguchi Tsutomu, Komatsu Shuhei, Ichikawa Daisuke, Hirajima Shoji, Nishimura Yukihisa, Konishi Hirotaka, Shiozaki Atsushi, Fujiwara Hitoshi, Okamoto Kazuma, Tsuda Hitoshi, Otsuji Eigo
1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
2 Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
Tumour Biol. 2017 Jun;39(6):1010428317700409. doi: 10.1177/1010428317700409.
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.
最近的研究表明，含三联基序的蛋白质家族的一些成员作为致癌作用的重要调节因子发挥作用。在本研究中，我们调查了含三联基序的蛋白质44是否通过其在食管鳞状细胞癌中的过表达而作为促癌基因发挥作用。我们分析了食管鳞状细胞癌细胞系以评估恶性潜能，并分析了68例原发性肿瘤以评估含三联基序的蛋白质44蛋白在食管鳞状细胞癌患者中的临床相关性。在食管鳞状细胞癌细胞系（8/14个细胞系；57%）和食管鳞状细胞癌原发性肿瘤样本（39/68例；57%）中检测到含三联基序的蛋白质44蛋白的表达。使用几种特异性小干扰RNA敲低食管鳞状细胞癌细胞中含三联基序的蛋白质44的表达可抑制细胞迁移和侵袭，但不抑制细胞增殖。免疫组织化学分析表明，肿瘤浸润区域中含三联基序的蛋白质44蛋白的过表达与淋巴结转移状态相关（p = 0.049），并且含三联基序的蛋白质44过表达肿瘤患者的总生存率明显低于非表达肿瘤患者（p = 0.029）。此外，多变量Cox回归模型确定含三联基序的蛋白质44蛋白的过表达是一个独立的不良预后因素（风险比 = 2.815；p = 0.041），以及淋巴浸润（风险比 = 2.735；p = 0.037）。这些结果表明，含三联基序的蛋白质44蛋白可能通过其过表达在肿瘤侵袭中发挥关键作用，并突出了其作为食管鳞状细胞癌预测指标和潜在治疗靶点的有用性。
