Prognostic significance of Versican expression in gastric adenocarcinoma.

X-H Shen,Q-Y Zhang,L Dong,P Qi,W-W Weng,W-Q Sheng,Y-Q Ma,S-J Ni,D Huang,C Tan,M-D Xu,X Du,Y-Q Wang,W-R Lin,W Zhang

doi:10.1038/oncsis.2015.36

Abstract

Gastric cancer (GC) is the leading malignancy in the digestive system. Versican is a ubiquitous component of the extracellular matrix and has a role in tumor progression. We aim to examine the expression of Versican in GC and the relationship between Versican levels and patient survival. We detected the mRNA expression of Versican in tumorous pairs and adjacent normal tissues (ANTs) of 78 GC patients by quantitative real-time polymerase chain reaction. The protein expression of Versican in 101 cases of matched GC and ANT, as well as in 27 intraepithelial neoplastic (IN) samples, was evaluated by immunohistochemistry. We analyzed the correlation between Versican levels and clinical outcomes. Finally, we performed CCK-8 cell counting assay and transwell assay in GC cell lines. Versican mRNA expression was significantly greater in tumor tissues (P<0.001) than in ANT. Versican was majorly expressed in the stroma surrounding tumor epithelium and minorly some areas of tumor epithelium. The Versican expression level was higher in GC than in ANT (P=0.004), but no significant difference was observed between ANT and IN (P=0.517). The Versican mRNA and protein levels were consistent in GC. High Versican mRNA and protein expression correlated with greater tumor invasion depth (P=0.030, P=0.027). Univariate and multivariate analysis revealed that patients with high Versican mRNA expression exhibited poor disease-specific survival (P<0.001). In vitro experiments showed that Versican overexpression promoted cell proliferation and invasion. Our data indicate that Versican may be a novel prognostic indicator in GC and may be a potential target for clinical diagnosis.

Highlights

It turned out that Versican expression was significantly greater in tumor tissues compared with adjacent normal tissues (ANTs; P o 0.001; Figure 1), suggesting that Versican was highly expressed in malignant gastric adenocarcinoma
33.00%; Figure 2g), the proportion of high Versican expression was significantly larger in gastric adenocarcinoma than that in either intraepithelial neoplastic (IN) (P = 0.004) or ANT (P = 0.000; Figure 2h)
Our study suggested that Versican expression was only detected in the tumor stroma surrounding epithelial lesions in gastric adenocarcinoma without any supplementary intracellular Versican accumulation, thereby suggesting that in Gastric cancer (GC), Versican is likely predominantly synthesized in the tumor stroma by stromal fibroblasts

Summary

Introduction

Gastric cancer (GC) remains one of the most common malignancies and most frequent cause of cancer death. The majority of GC is gastric adenocarcinoma, which has a relatively high 5-year survival rate despite of the early-stage diagnosis. Clinical prognostic factors such as histological type and stage supply limited predictive information for the subsequent treatment of gastric adenocarcinoma, and new biological markers are in demand to achieve the most effective diagnostic method.The extracellular matrix (ECM), composed of proteoglycans (PGs), glycoproteins and collagens, is a highly organized structure with many physiological and pathological roles. Modifying the ECM composition through a large array of molecules, as well cell–cell and cell–matrix interactions, may be crucial for tumor initiation and progression. PGs, a group of heavily glycosylated proteins, are present throughout the mammalian body and are involved in a wide variety of biological phenomena, including structural maintenance, tissue remodeling, molecular presentation, cellular adhesion and signal transmission. The majority of GC is gastric adenocarcinoma, which has a relatively high 5-year survival rate despite of the early-stage diagnosis.. The majority of GC is gastric adenocarcinoma, which has a relatively high 5-year survival rate despite of the early-stage diagnosis.1 Clinical prognostic factors such as histological type and stage supply limited predictive information for the subsequent treatment of gastric adenocarcinoma, and new biological markers are in demand to achieve the most effective diagnostic method. A member of the aggregating chondroitin sulfate PGs family, is accumulated predominantly in the tumor stroma, providing hygroscopic properties to create a loose and hydrated matrix that is necessary to support key events in development and disease. Through direct or indirect interactions with cells and molecules, Versican has significant roles in modulating cell proliferation, differentiation, adhesion and migration, all of which are features of cancer invasion and metastasis.. Through direct or indirect interactions with cells and molecules, Versican has significant roles in modulating cell proliferation, differentiation, adhesion and migration, all of which are features of cancer invasion and metastasis. Versican may serve a wide range of functions in the invasion and metastasis of tumor cells

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