Arita Hidetaka, Nagata Masashi, Yoshida Ryoji, Matsuoka Yuichiro, Hirosue Akiyuki, Kawahara Kenta, Sakata Junki, Nakashima Hikaru, Kojima Taku, Toya Ryo, Murakami Ryuji, Hiraki Akimitsu, Shinohara Masanori, Nakayama Hideki
1 Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
2 Department of Radiation Oncology, Kumamoto University Hospital, Kumamoto, Japan.
Tumour Biol. 2017 Oct;39(10):1010428317731771. doi: 10.1177/1010428317731771.
FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.
FBXW7（含F-box和WD重复结构域蛋白7）是一种肿瘤抑制蛋白，在多种恶性肿瘤中调节多种癌蛋白的降解。然而，关于FBXW7在口腔鳞状细胞癌中的表达信息有限。因此，本研究旨在确定FBXW7表达在口腔鳞状细胞癌中的临床意义。采用定量实时聚合酶链反应和免疫组织化学染色，评估了15例行根治性切除患者的口腔鳞状细胞癌组织及癌旁正常组织中FBXW7的表达模式。此外，对110例接受基于5-氟尿嘧啶的放化疗后手术的口腔鳞状细胞癌患者活检标本的石蜡包埋切片进行免疫组织化学检测。评估这些患者中FBXW7表达与各种临床病理特征及预后的相关性。结果显示，在15对匹配样本中，口腔鳞状细胞癌组织中FBXW7的表达明显低于癌旁正常组织。在临床病理分析中，与高蛋白表达相比，低FBXW7表达与术前放化疗的组织学反应差显著相关。Kaplan-Meier曲线分析显示，低FBXW7表达与预后不良显著相关，多因素分析发现FBXW7表达是总生存的独立预测因素。我们的结果表明，FBXW7可能在口腔鳞状细胞癌中发挥肿瘤抑制蛋白的作用。此外，FBXW7不仅可能是预测口腔鳞状细胞癌患者放化疗临床反应的潜在生物标志物，也是预测总生存的潜在生物标志物。
