Significance And Relationship Between The Expression Of Human Telomerase Reverse Transcriptase Gene And Cell Cycle Regulators In Gastric Cancer

Objective To investigate the significance and expression of human telomerase reverse transcriptase gene(hTRT) in gastric cancer(GC) and its correlations with cell cycle regulators including P16INK4, cyclinDl , P21WAF1 and P53. Methods In situ hybridization(ISH) for hTRT mRNA was performed in 53 cases of gastric cancer and adjacent tissues. Immunohistochemical staining( S-P method) for hTRT protein, P16INK4, cyclinDl , P21WAF1 and P53 were performed in 53 cases of GC and adjacent tissues. Results 1. Of 53 cases of GC, the expression of hTRT mRNA and hTRT protein were significantly higher than those in adjacent tissues. There was a stastical difference of the expression of hTRT protein among well differentiated adenocarcinoma, poor differentiated adenocarcinoma and mucoid carcinoma. And there was a highly significant positive correlation between the expression of hTRT mRNA and hTRT protein. However, the expression of hTRT mRNA and its protein in GC were not related with other clinicopathological parameters including gender, age, location and size of neoplasm, wall invasion, lymph node metastasis and clinical stage. 2. Of 53 cases of GC, the expression of cyclinDl and P53 protein were significantly higher than those in adjacent tissues; the expression of P16INK4 and P21WAF1 protein were significantly lower than those in adjacent tissues. The positive percent of P16INK4 protein was significantly related with the depth of tumor invasion and lymph node metastasis. There was a stastical difference of the expression of P53 protein among well differentiated adenocarcinoma, poor differentiated adenocarcinoma and mucoid carcinoma. 3. There was a significant positive correlation between the expression of hTRT mRNA and cyclinDl protein, while the expression of hTRT mRNA wasnegatively correlated with P21WAF1. There was a significant positive correlation between the expression of cyclinDl protein and hTRT protein, so was P53 and hTRT protein.4. Multivariate Cox regression analysis indicated that lymph node matastasis and the expression of P16INK4 protein were independent prognostic factors which affected survival in GC. Conclusion 1. The expression of hTRT gene is correlated significantly to specific defects of cell cycle on Gl/S check point ; telomerase activity may depends on cell cycle in gastric cancer and it is available to clarify the molecular mechanism of telomerase activity regulation. 2.The expression of hTRT mRNA, hTRT protein, P16INK4 protein, cyclinDl protein, P21WAF1 and P53 protein in GC are significantly different from those in adjacent tissue which indicate that these targets are correlated closely to the occurrence of GC and can provide important methods of morphology for diagnosis of GC. 3. It is helpful for predicting the prognosis and giving the assistant treatment of patients with GC to detect the expression of P16INK4 protein.