Stathmin is a Marker of Progression and Poor Prognosis in Esophageal Carcinoma

Abstract

Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression.. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.

STMN1 overexpression correlates with biological behavior in human cutaneous squamous cell carcinoma

“…Nie et al [19] found that increased STMN1 expression was observed non-small cell lung cancer, and high expression of STMN1 protein was tightly related to poor tumor differentiation, large tumor size, advanced N stage, and advanced TNM stage, implying STMN1 may play a critical role in the progression of NSCLC and may serve as a useful prognostic biomarker of the patients with NSCLC. In addition, Wang et al [18] demonstrated that significantly increased STMN1 protein expression was observed in were 73.0% in esophageal carcinoma tissues and 30.0% in the corresponding normal esophageal mucosa tissues, and further investigation found that increased STMN1 expression was significantly correlated with tumor differentiation, lymph node metastasis, TNM clinical classification and tumor invasion distant metastasis, suggesting that STMN1 might be essential in conferring a more aggressive behavior in esophageal carcinoma.…”

“…Numerous studies have noted that the constitutive activation and overexpression of STMN1 were associated with a variety of human malignancies, including acute leukemia [12], nasopharyngeal carcinoma [13], hepatocellular carcinoma [14], gastric cancer [15], cervical carcinoma [16], colorectal cancer [17] and esophageal squamous cell carcinoma [18]. Nie et al [19] found that increased STMN1 expression was observed non-small cell lung cancer, and high expression of STMN1 protein was tightly related to poor tumor differentiation, large tumor size, advanced N stage, and advanced TNM stage, implying STMN1 may play a critical role in the progression of NSCLC and may serve as a useful prognostic biomarker of the patients with NSCLC.…”

Overexpression of stathmin promotes metastasis and growth of malignant solid tumors: a systemic review and meta-analysis

“…Subsequently, we performed a series of subgroup analysis and found that stathmin displayed a higher expression in advanced cancers, poor differentiated cancers and cancers with lymphatic metastasis, which implied that stathmin intimately involved in tumor cell differentiation, proliferation and invasion of tumors. Metastasis and invasion are the critical factors in the progression of cancer, stathmin has been reported intimately correlating with malignant behavior of tumors [5, 8, 9, 22, 38–41] and affect the survival of tumor patients. In our study, we noticed that patients who exhibited high expressions of stathmin had a significantly shorter post-surgical survival time (27.93 ± 11.54 months) compared with patients who exhibited moderate and low expressions of stathmin (44.81 ± 15.82 months).…”

Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

“…At the molecular level, Stathmin 1 depolymerizes microtubules by either sequestering free tubulin dimers or directly inducing microtubule-catastrophe [31]. As mentioned before, Stathmin 1 is encoded by the human STMN1 gene, which has 4 serine phosphorylation sites.…”