High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma

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

doi:10.3892/ijo.2017.3899

High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma

Authors:
- Shigemasa Suzuki
- Takehiko Yokobori
- Bolag Altan
- Keigo Hara
- Daigo Ozawa
- Naritaka Tanaka
- Makoto Sakai
- Akihiko Sano
- Makoto Sohda
- Halin Bao
- Minoru Fukuchi
- Tatsuya Miyazaki
- Kyoichi Kaira
- Takayuki Asao
- Hiroyuki Kuwano
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Affiliations: 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, Big Data Center for Integrative Analysis, Gunma University Initiative for Advance Research (GIAR), Gunma, Japan
Published online on: March 7, 2017 https://doi.org/10.3892/ijo.2017.3899
Pages: 1184-1190

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Abstract

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.

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