Kumakura Yuji, Rokudai Susumu, Iijima Misaki, Altan Bolag, Yoshida Tomonori, Bao Halin, Yokobori Takehiko, Sakai Makoto, Sohda Makoto, Miyazaki Tatsuya, Nishiyama Masahiko, Kuwano Hiroyuki
Department of General Surgical Science, Gunma University, Maebashi, Japan.
Department of Molecular Pharmacology and Oncology, Gunma University, Maebashi, Japan.
Cancer Sci. 2017 Nov;108(11):2149-2155. doi: 10.1111/cas.13394. Epub 2017 Oct 3.
This study aims to explore the expression level of ΔNp63 in esophageal squamous cell carcinoma (ESCC). To investigate the association between ΔNp63 (p40) expression and ESCC biology, we compared the levels of ΔNp63 expression in normal and tumor tissues, with a specific focus on the diagnostic value of ΔNp63 in ESCC. We analyzed 160 consecutive patients with ESCC who underwent surgical resection without neoadjuvant chemotherapy at Gunma University Hospital (Maebashi, Japan) between September 2000 and January 2010. The clinicopathological characteristics and survival of patients were subclassified based on the expression of ΔNp63 as determined by immunohistochemistry, indicating that ΔNp63 was highly expressed in 75.6% (121/160) of ESCC patients. Clinicopathological analysis of ΔNp63 expression showed that ΔNp63-positive tumors significantly correlated with two important clinical parameters: T factor (P = 0.0316) and venous invasion (P = 0.0195). The 5-year overall survival rates of advanced ESCC patients with positive and negative expression of ΔNp63 were 35.6% and 71.7%, respectively. Multivariate analysis revealed that the expression of ΔNp63 was identified as an independent prognostic factor (P = 0.0049) in advanced ESCC. In line with this, ΔNp63α-transduced ESCC cell lines increased tumor growth in a soft agar colony formation assay. We report here for the first time that ΔNp63 expression increases the oncogenic potential of ESCC and is an independent marker for predicting poor outcome in advanced ESCC. Our findings suggest that ΔNp63 could serve as a new diagnostic marker for ESCC and might be a relevant therapeutic target for the treatment of patients with this disease.
本研究旨在探讨ΔNp63在食管鳞状细胞癌（ESCC）中的表达水平。为了研究ΔNp63（p40）表达与ESCC生物学行为之间的关联，我们比较了正常组织和肿瘤组织中ΔNp63的表达水平，特别关注ΔNp63在ESCC中的诊断价值。我们分析了2000年9月至2010年1月期间在群马大学医院（日本前桥）接受手术切除且未接受新辅助化疗的160例连续ESCC患者。根据免疫组织化学检测确定的ΔNp63表达情况，对患者的临床病理特征和生存情况进行了亚分类，结果显示75.6%（121/160）的ESCC患者中ΔNp63呈高表达。对ΔNp63表达的临床病理分析表明，ΔNp63阳性肿瘤与两个重要临床参数显著相关：T因子（P = 0.0316）和静脉侵犯（P = 0.0195）。ΔNp63表达阳性和阴性的晚期ESCC患者的5年总生存率分别为35.6%和71.7%。多因素分析显示，ΔNp63的表达被确定为晚期ESCC的独立预后因素（P = 0.0049）。与此一致的是，在软琼脂集落形成试验中，转导了ΔNp63α的ESCC细胞系增加了肿瘤生长。我们首次在此报告，ΔNp63表达增加了ESCC的致癌潜能，并且是预测晚期ESCC预后不良的独立标志物。我们的研究结果表明，ΔNp63可作为ESCC的一种新的诊断标志物，并且可能是该病患者治疗的一个相关治疗靶点。
