Abstract
BackgroundS100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression.MethodsS100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated.ResultsS100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells.ConclusionsOur results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis.
Highlights
S100A9 was originally discovered as a factor secreted by inflammatory cells
Expression of S100A9 in infiltrating inflammatory cells in gastric cancer and chronic gastritis tissues In a previous gene array analysis, we found that gastric cancer tissues were distinguished from adjacent noncancerous mucosa by characteristic differences in their gene expression patterns [26]
Immunohistochemistry of specimens from 177 gastric cancer patients showed that S100A9 was positive in all primary cancer tissues with immunostaining exclusively located in inflammatory cells such as macrophages and neutrophils infiltrating primary tumor tissues (The different cell types in tissue samples were identified by two independent pathologists) (Figure 1B)
Summary
S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. Discovery of new biomarkers aiding in early detection and accurate prediction of tumor behavior could improve patient survival [4,5,6]. Members of the S100 family of proteins are emerging as biomarkers in multiple types of tumors [7]. S100A9 expression is up-regulated in tumor cells in lung [16], prostate [17], and breast cancer [18,19], while it is down-regulated in human esophageal cancer cells [20]. In colorectal cancer tissue specimens, the S100A9 protein was not detected in cancer cells, but rather in inflammatory cells scattered throughout the tumor stroma [21]. Gene expression and proteomic analysis demonstrated high expression of S100A9 in the tissue. Its distribution within the tissue and association with clinicopathological features were not fully demonstrated
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