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.
Highlights
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a significant mortality rate [1,2]
The immunoexpression of Stathmin 1 (STMN1) was stronger in the marginal regions of primary ESCCs than in the main tumor or surrounding normal tissues (Fig. 1A and B)
The 5-year disease-specific survival rate was significantly reduced in ESCC patients with high STMN1 expression compared to those with low STMN1 expression (49.5 vs. 73.9%, respectively; P= 0.002; Fig. 1E)
Summary
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a significant mortality rate [1,2]. STMN1 expression correlates with tumor progression and poor prognosis in various cancers [7,8,9,10,11,12,13,14,15,16,17] including ESCC [18]. These studies indicated that STMN1 is a fundamental cancer-associated gene and a potential target for the diagnosis and treatment of cancers, including ESCC. The exact significance of STMN1 in tumor progression and therapeutic resistance has not yet been elucidated in ESCC patients treated with CRT
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