Abstract
BackgroundThrombospondin1 (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis. The purpose of this study is to explore the expression and prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC).MethodsWe used immunohistochemistry and western blotting to examine the expression status of THBS1, Cyr61 and CTGF in ESCC. Correlations of THBS1, Cyr61 and CTGF over-expressions with various clinicopathologic factors were also determined by using the Chi-square test or Fisher's exact probability test. Survival analysis was assessed by the Kaplan-Meier analysis and the log-rank test. Relative risk was evaluated by the multivariate Cox proportional hazards model.ResultsTHBS1, Cyr61 and CTGF were all over-expressed in ESCC. THBS1 over-expression was significantly associated with TNM stage (P = 0.029) and regional lymph node involvement (P = 0.026). Kaplan-Meier survival analysis showed that over-expression of THBS1, Cyr61 or CTGF was related to poor survival of ESCC patients (P = 0.042, P = 0.020, P = 0.018, respectively). Multivariate Cox analysis demonstrated that Cyr61 and CTGF were independent factors in prognosis of ESCC.ConclusionCyr61, CTGF and THBS1 were all over-expressed in ESCC and might be new molecular markers to predict the prognosis of ESCC patients.
Highlights
Thrombospondin1 (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis
TGF-β signaling pathway can be activated by thrombospondin1 (THBS1) through its interaction with latent TGF-β binding proteins (LTBP) so that TGF-β is capable of binding to its receptors and stimulating the
To further explore the expression patterns of THBS1, Cyr61 and CTGF and determine whether these proteins could be prognostic factors in esophageal squamous cell carcinoma (ESCC), we investigated their expressions in a series of ESCC by using immunohistochemistry staining and western blotting
Summary
Thrombospondin (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis. Diagnosis of ESCC at its early stage still remains difficult and advanced ESCC frequently displays local invasion and (page number not for citation purposes) lymph node metastasis, which is one of the important reasons for its poor prognosis [2]. The development of this malignancy rises from the stepwise accumulations of multiple genetic alterations, leading to the activation of oncogenes and/or the inactivation of tumor suppressor genes. TGF-β signaling pathway can be activated by thrombospondin (THBS1) through its interaction with latent TGF-β binding proteins (LTBP) so that TGF-β is capable of binding to its receptors and stimulating the
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