High-Level Expression of S100A4 Correlates with Lymph Node Metastasis and Poor Prognosis in Patients with Gastric Cancer

Abstract

The present study investigated the clinical significance of S100 calcium binding protein A4 in the development, progression, and metastasis of gastric cancer. Tumor tissue, adjacent normal tissue, and lymph node and peritoneal metastases were obtained from patients with gastric cancer, and their gene expression profiles were analyzed by Affymetrix GeneChip HG-U133A2.0 array. The expression of S100A4 was detected by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in gastric tumor tissue and lymph node and peritoneum metastasis. Immunohistochemistry was employed to analyze S100A4 expression in 436 clinicopathologically characterized gastric cancer cases and in corresponding distant metastases from 61 patients. A total of 434 genes and 169 expressed sequence tags were upregulated by at least twofold in the tumor tissue. The expression of S100A4 in lymph node and peritoneal metastases was significantly higher than that in gastric tumor tissue. The expression of S100A4 messenger RNA (mRNA) or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node and peritoneal metastases. Further multivariate analysis suggested that depth of invasion, lymph node and distant metastases, tumor-node-metastasis (TNM) stage, and upregulation of S100A4 were independent prognostic indicators for the disease. Gene expression profiles are a useful way to perform simultaneously large-scale analysis of the expression level of thousands of genes. Expression of S100A4 in gastric cancer is associated significantly with lymph node and distant metastases, and poor prognosis. S100A4 may be a useful marker to predict development, progression, and metastasis of gastric cancer.