High TGFBI expression in ESCC tissues could be a powerful biomarker of poor prognosis and hematogenous recurrence. TGFBI in stromal cells might be a promising molecular target for ESCC treatment.
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.
IntroductionEsophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a significant mortality rate (1,2). Despite improvements in the surgical management of ESCC and development of useful chemotherapies and chemoradiotherapies (CRTs), the prognosis of patients with advanced disease remains poor (3-5). Furthermore, the identification of novel therapeutic targets is essential for individual curative adjuvant or neoadjuvant therapies.Stathmin 1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics by preventing tubulin polymerization and promoting microtubule destabilization (6). STMN1 is highly expressed in multiple human malignancies and is therefore also known as oncoprotein 18. STMN1 expression correlates with tumor progression and poor prognosis in various cancers (7-17) 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. However, the exact significance of STMN1 in tumor progression and therapeutic resistance has not yet been elucidated in ESCC patients treated with CRT.The expression of STMN1 is known to be functionally linked to chemosensitivity to microtubule-stabilizing agents such as taxanes, which are widely used anticancer agents. Inhibiting STMN1 expression enhances chemosensitivity to paclitaxel in osteosarcoma cells (19) and ESCCs (20) in vitro, while the overexpression of STMN1 decreases breast cancer cell sensitivity to paclitaxel and vinblastine (7). In Japan, docetaxel is con...
Our data suggest that high expression of PROX1 in ESCC could be used as an indicator of poor prognosis, and that PROX1 is a promising candidate molecular target for ESCC treatment.
Tumor necrosis factor α induced protein 3 (TNFAIP3) is a protein that is induced by TNF-mediated NF-κB activation and has a dual function in regulating NF-κB. TNFAIP3 is associated with inflammatory carcinogenesis in many cancer types. However, the clinical significance of TNFAIP3 expression and function in esophageal squamous cell carcinoma (ESCC) has not yet been reported. We examined 149 ESCC tissue specimens to determine the clinical significance of TNFAIP3 by immunohistochemistry. Western blot analyses were used to detect TNFAIP3 expression in TE-1, TE-8, TE-15 and KYSE-70 ESCC cells and in Het-1A, a non-cancerous esophageal cell line. TNFAIP3 protein knockdown was conducted using small-interfering RNA to investigate its impact on cell proliferation, migration and invasion. Significant correlations between TNFAIP3 expression and differentiation (P=0.04) among clinicopathological characteristics of ESCC patients were demonstrated, and high TNFAIP3 expression was associated with poor survival (P=0.02). Moreover, multivariate analysis result showed that high TNFAIP3 expression was an independent factor for poor survival (P=0.04). In vitro analysis showed high expression of TNFAIP3 protein in TE-15 cells and low expression in Het-1A cells. Furthermore, the proliferation, migration and invasion of TE-15 cells after TNFAIP3 suppression by siRNA were significantly reduced. These findings suggest that TNFAIP3 protein may be an independent prognostic marker for poor survival, and a promising target for ESCC therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.