Abstract
BackgroundThe correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival.MethodsTissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC in vitro.ResultsSkp2 expression correlated closely with the T category (p = 0.035) and the pathological tumor-node-metastasis (TNM) stage (p = 0.027). High expression of Skp2 was associated with poor overall survival in resectable ESCC (p = 0.01). The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. In vitro assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs.ConclusionsNegative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.
Highlights
The correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial
No statistically significant correlation was observed between Skp2 expression and age, sex, tumor location, histological grade, or N categories (Table 1), but the Skp2 expression correlated closely with the T category (p = 0.035) and the pathological American Joint Committee on Cancer (AJCC) stage (p = 0.027)
The effect of Skp2 on cell proliferation in ESCC cells Because the expression of Skp2 significantly correlated with the T category and overall survival, we proposed that Skp2 could play a functional role in the cell proliferation of ESCC
Summary
The correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp on survival. Squamous cell carcinoma is the most common pathological esophageal cancer in the East [1], and surgery is still the best curative treatment option [2]. One of the key players regulating cell cycle progression is the F-box protein, Skp (S-phase kinase– associated protein 2) [8,9]. The correlation of Skp expression with metastasis and prognosis in ESCC is still controversial [15,16]
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