Overexpression of protease inhibitor-associated gene in human gastric carcinoma and its clinicopathological significance Free

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Gastric cancer is the second most common cancer in the world and the 5th leading cause of cancer-related death in Taiwan. To improve the survival of gastric cancer patients, biomarkers for early detection and effective anti-cancer therapy are required. cDNA microarrays were performed to identify genes that are aberrantly expressed in gastric cancer. The clinicopathologic correlation and prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of gastric cancer. Protease inhibitor-associated (PIA) gene, one of the most highly-expressed genes in both intestinal and diffuse gastric cancers in our microarray results, was selected for further study. Fresh surgical samples of tumor tissue and matching non-cancerous mucosa were obtained immediately after gastric resection in 60 patients. The PIA mRNA transcripts and proteins were also over-expressed in gastric cancer cells. The expression of PIA in tumor tissues was, on average, 8.47-fold increased compared to adjacent non-cancerous mucosa. The expression of PIA was higher in advanced (T2, T3 and T4) cancer compared to the early (T1) cancer (p = 0.001) with regard to depth of wall invasion. Higher expression of PIA was significantly associated with lymph node metastasis (p < 0.001), and lymphatic invasion (p = 0.004). Expression of PIA in patients in stage II and above, was significantly higher than those in stage I (p = 0.001). The 5-year survival of patients with lower expression of PIA was significantly better than those with a higher expression (log rank p = 0.0296). To further understand the role of PIA gene in the human gastric cancer cells, the PIA-over-expressing AZ521 isogenic cell lines were prepared. The expression levels of PIA gene were confirmed by Q-RT-PCR and immuno-histochemical staining. The cell growth rate was increased about 2-3 fold in the PIA over-expressing lines. Our results indicate that the PIA can be used as a potential prognostic marker for gastric cancer. Its function is related the cell proliferation.