Suzuki Shigemasa, Yokobori Takehiko, Altan Bolag, Hara Keigo, Ozawa Daigo, Tanaka Naritaka, Sakai Makoto, Sano Akihiko, Sohda Makoto, Bao Halin, Fukuchi Minoru, Miyazaki Tatsuya, Kaira Kyoichi, Asao Takayuki, Kuwano Hiroyuki
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Int J Oncol. 2017 Apr;50(4):1184-1190. doi: 10.3892/ijo.2017.3899. Epub 2017 Mar 7.
Stathmin 1 (STMN1) is a major cytosolic phosphoprotein regulating microtubule dynamics, thereby playing an important role in cancer progression and resistance to microtubule-binding anticancer agents. We assessed the prognostic significance of STMN1 expression and STMN1-associated resistance to docetaxel and radiation in esophageal squamous cell carcinoma (ESCC) patients. STMN1 expression was evaluated by immunohistochemistry in 172 surgical specimens. The association of STMN1 expression with chemoradiation resistance using docetaxel was examined by comparing expression in 15 biopsy specimens obtained before neoadjuvant therapy to histological grades of post-therapy surgically resected tumors. We also evaluated the effects of STMN1 on sensitivity to docetaxel and radiation in ESCC cell lines. High STMN1 immunoexpression was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion and venous invasion. Survival rates were significantly lower in ESCC patients with high STMN1 expression than in those with low STMN1 expression. Multivariable analysis showed that high STMN1 expression was an independent factor for poor survival. High STMN1 expression was also associated with poor response to neoadjuvant chemoradiotherapy using docetaxel. Knockdown of STMN1 expression enhanced ESCC cell line sensitivity to docetaxel and radiation. STMN1 appears critical for ESCC invasiveness and predicts an unfavorable prognosis in ESCC.
Stathmin 1（STMN1）是一种主要的胞质磷蛋白，可调节微管动力学，从而在癌症进展以及对微管结合抗癌药物的耐药性方面发挥重要作用。我们评估了STMN1表达以及STMN1相关的对多西他赛和放疗的耐药性在食管鳞状细胞癌（ESCC）患者中的预后意义。通过免疫组织化学方法对172例手术标本中的STMN1表达进行了评估。通过比较新辅助治疗前获得的15例活检标本中的表达与治疗后手术切除肿瘤的组织学分级，研究了STMN1表达与使用多西他赛的放化疗耐药性之间的关联。我们还评估了STMN1对ESCC细胞系对多西他赛和放疗敏感性的影响。高STMN1免疫表达与肿瘤深度、淋巴结转移、淋巴浸润和静脉浸润显著相关。STMN1高表达的ESCC患者的生存率显著低于STMN1低表达的患者。多变量分析表明，高STMN1表达是生存不良的独立因素。高STMN1表达还与使用多西他赛的新辅助放化疗反应不佳相关。敲低STMN1表达可增强ESCC细胞系对多西他赛和放疗的敏感性。STMN1似乎对ESCC的侵袭性至关重要，并可预测ESCC的不良预后。
