Expression Of Caspase-9 And Bax And Its Relationship To Apoptosis In Gastric Carcinoma

Objective:Gastric carcinoma is the very common digestive tract tumor. With the research of gastric carcinoma`s development furthering, it has been discovered that the development of gastric carcinoma is in close relation with apoptosis. At present, research on gastric carcinoma cell apoptosis and its regulatory mechanism has been one of the highlights in medical field. In this study, immunohistochemistry SP (Streptavidin Peroxdase Conjugated Method) was used to detect Caspase-9 and Bax in gastric carcinoma and without gastric carcinoma tissue.TUNEL(Terminal Deoxynucleotidyl Transferase )method was employed to detect the apoptosis in gastric carcinoma cells and without gastric carcinoma cells. Furthermore, we evaluated the function of Caspase-9 and Bax in gastric carcinoma. And their relationships with apoptosis were also analyzed.Methods:Immunohistochemistry SP was used to detect the expression of Caspase-9 and Bax in 57 patients with gastric carcinoma and 47 patients without gastric carcinoma. And the relationships between the expression of Caspase-9 and Bax with clinical pathological characteristics were evaluated. Tumor cell apoptosis was detected with TUNEL method.Results:1.The expression of Caspase-9 and Bax in gastric carcinoma and without gastric carcinoma tissue(1) The positive expression of Caspase-9 protein in gastric carcinoma was 40.35% which significantly lower than 70.83% in without gastric carcinoma (P﹤0.05). The positive expression of Bax protein in gastric carcinoma was 35.09% which significantly lower than 72.92% in without gastric carcinoma (P﹤0.05).(2) The positive expression of Caspase-9 protein in without gastric carcinoma tissue including chronic superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia was 100.00%, 86.67%, 50.00% and 42.85% respectively, which demonstrated the decreasing tendency (P﹤0.05). The positive expression of Caspase-9 protein in chronic superficial gastritis was significantly higher than in intestinal metaplasia and atypical hyperplasia (P﹤0.05). The positive expression of Caspase-9 protein in intestinal metaplasia was higher than in atypical hyperplasia but there was no significant difference (P﹥0.05).(3) The positive expression of Bax protein in without gastric carcinoma tissue including chronic superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia was 100.00%,80.00%,56.25% and 57.14% respectively, which demonstrated the decreasing tendency. The positive expression of Bax protein in chronic superficial gastritis was significantly higher than in intestinal metaplasia and atypical hyperplasia (P﹤0.05).2.The relationships between Caspase-9 and different clinical characteristics of gastric carcinoma(1) The positive expression of Caspase-9 protein in gastric carcinoma tissue including well and moderately differentiated adenocarcinoma, poorly differentiated adenocarcinoma, mucinous carcinoma was 64.28%,32.35%,33.33% respectively. The positive expression of Caspase-9 protein in well and moderately differentiated adenocarcinomas were significantly higher than poorly differentiated adenocarcinoma and mucinous carcinoma (P﹤0.05). The positive expression of Caspase-9 protein in poorly differentiated adenocarcinoma was lower than mucinous carcinoma but there was no significant difference (P﹥0.05).(2) The positive expression of Caspase-9 protein in metastasized and non-metastasized lymph node were 39.02% and 43.75%, and no significant difference was found (P﹥0.05).(3) The positive expression of Caspase-9 protein in clinical stageⅢ-Ⅳgastric carcinoma andⅠ-Ⅱgastric carcinoma were 38.46% and 44.44%, and there was no significant difference (P﹥0.05).(4) The positive expression of Caspase-9 protein in tissues in whichmucosa was infiltrated but serosa was not infiltrated by gastric carcinomas was 41.67%. The positive expression of Caspase-9 protein in tissues in which both mucosa and serosa were infiltrated by gastric carcinomas was 40.00%. And there was no significant difference (P﹥0.05).(5) The positive expression of Caspase-9 protein in tumors more than 5 cm and less than 5 cm were 45.83% and 36.36%, and there was no significant difference (P﹥0.05).3.The relationship between Bax and different clinical characteristics of gastric carcinoma(1) The positive expression rate of Bax protein in gastric carcinoma tissue including well and moderately differentiated adenocarcinoma, poorly differentiated adenocarcinoma, mucinous carcinoma was 57.14%, 26.47%, 33.33% respectively. The rate in the well and moderately differentiated adenocarcinoma was significantly higer than poorly differentiated adenocarcinoma and mucinous carcinoma (P﹤0.05). The rate in poorly differentiated adenocarcinoma was lower than mucinous carcinoma but there was no significant difference between them (P﹥0.05).(2) The positive expression of Bax protein in metastasized and non-metastasized lymph node were 31.71% and 43.75%, and there was no significant difference (P﹥0.05).(3) The positive expression of Bax protein in clinical stageⅢ-ⅣandⅠ-Ⅱwere 30.77% and 44.44%, and there was no significant difference (P﹥0.05).(4) The positive expression of Bax protein in tissues in which mucosa was infiltrated but serosa was not infiltrated by gastric carcinomas was 33.33%, The positive expression of Bax protein in tissues in which both mucosa and serosa were infiltrated by gastric carcinomas was 41.67%. And there was no significant difference (P﹥0.05).(5) The positive expression of Bax protein more than 5 cm and less than 5 cm were 25.00% and 42.42%, and there was no significant difference (P﹥0.05).4.The relevance of Caspase-9 and Bax gastric carcinoma tissueIn 23 cases which Caspase-9 expressed positive in gastic carcinoma Bax expressed positive in 17 cases. In 37 cases which Bax expressed negative in gastic carcinoma Caspase-9 expressed negative 31 cases, Caspase-9 isassociated with Bax (P﹤0.05).5.Using TUNEL method in tumor tissue and non-tumor tissue(1) The apoptosis index in chronic superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia and gastric carcinoma were 14.72±2.68%, 10.02±2.34%,7.55±2.80%, 6.09±2.35%, and3.26±1.23%, which demonstrated the decreasing tendency and the difference was significant (P﹤0.05).(2) The apoptosis index in patients with the positive expression of Caspase-9 was significantly higher than with the negative expression (11.20±3.39% Versus 6.22±2.45%, P﹤0.05). The apoptosis index in patients with the positive expression of Bax was significantly higher than with the negative expression (12.54±3.60% Versus 7.18±1.25%, P﹤0.05).(3) The apoptosis index in patients with well and moderately differentiated adenocarcinoma, poorly differentiated adenocarcinoma, mucinous carcinoma was 5.72±1.25 % ,2.54±0.98 % ,and3.28±1.42 % respectively, and there was significant difference between the former and the last two(P﹤0.05).Conclusion :This study, by compared different pathological gastric carcinoma and non-tumor tissue for the expression of Caspase-9 and Bax protein, as well as related cellular apoptosis, demonstrated the following results:(1) Caspase-9 and Bax protein were lower in patients with gastric carcinoma, and may be related to the occurrence of tumor.(2) Caspase-9and Bax protein took part in the formation of precancerous lesion, and accelerate the occurrence of gastric carcinoma.(3) Caspase-9 and Bax protein became lower companying the decrease of tumor malignancy, and may be related to malignancy or benignity of tumor.(4) The apoptosis index in positive expression of Caspase-9 and Bax protein was higher than negative. It may suggest Caspase-9 and Bax protein take part in the process cellular apoptosis.(5) In gastric carcinoma Caspase-9 and Bax expression had the obvious relevance, we extrapolated that the suppression of Bax activating Caspase-9 plastochondria channel possibly took part in the gastric carcinoma occurrence.