Correlation Among The Expression Of MDR Proteins, Hemoglobin Concentration And The Expression Of HIF-1α In Gastric Cancer

Objective To detect the expression of P-glycoprotein (P-gp), topoisomerase-Ⅱ(TOPO-Ⅱ), glutathione-S-transferase-pi(GST-π) and hypoxia-inducible factor-1 alpha(HIF-1α) in gastric cancer and to investgate the correlation and possible mechanism among the expression of different multidrug resistance(MDR) proteins, hemoglobin(Hb) concentration and the expression of HIF-1α.Methods Fifty-six cases of tissue samples of gastric cancer and twenty cases of pericarcinoma normal mucosa tissue samples were examined for expression of P-gp, TOPO-Ⅱ, GST-π, HIF-1αby immunohistochemistry method. Gray scale was determined by PIPS-2020 colorful pathology analysis system, and the expression level of protein was expressed by mean gray scale(the lower gray scale, the higher the expression level of protein). To analyze the relationship between the expression of P-gp, TOPO-Ⅱ, GST-πand respective clinical pathological parameters(sex, age, Hb concentration, tumor invasion depth, histological type, lymph nodes metastasis) and to explore the correlation and possible mechanism among the expression of above three MDR proteins, Hb concentration and the expression of HIF-1α.Results (1)The expression of P-gp,GST-πand HIF-1αin gastric cancer was significantly higher than pericarcinoma normal mucosa tissues(P=0.002, 0.029, 0.003, <0.05) while the expression of TOPO-Ⅱwas significantly lower than pericarcinoma normal mucosa tissues(P=0.028, <0.01). (2)In gastric cancer, the expression of P-gp, GST-πwas correlated with histological type(P=0.007, 0.020, <0.05), but had no relationship with lymph nodes metastasis, invasion depth(P>0.05). The expression of HIF-1αwas correlated with lymph nodes metastasis(P=0.041, <0.05), invasion depth(P=0.032, <0.05), but had no relationship with histological type(P>0.05). The expression of TOPO-Ⅱwas not related with histological type, tumor invasion depth, lymph nodes metastasis(P>0.05). There was no relationship among the expression of P-gp, TOPO-Ⅱ, GST-π, HIF-1αin different sexual or age(P>0.05). (3)In gastric cancer, the expression of P-gp, GST-πand HIF-1αwere positive correlation with Hb concentration (P=0.011, 0.043, 0.005, <0.05, r=0.336, 0.271, 0.373), the expression of TOPO-Ⅱwas negative correlation with Hb concentration(P=0.029, <0.05, r=-0.292). The expression of P-gp was positive correlation with GST-π(P=0.043, <0.05, r=0.271) and HIF-1α(P=0.010, <0.05, r= 0.343). There was no significant correlation between the expression of P-gp/GST-πand TOPO-Ⅱand between the expression of TOPO-Ⅱ/GST-πand HIF-1α(P>0.05).Conclusion(1)The expression of P-gp, GST-πand HIF-1αin gastric cancer is higher than pericarcinoma normal mucosa tissues while the expression of TOPO-Ⅱis lower than pericarcinoma normal mucosa tissues.(2)In gastric cancer, the expression of P-gp, GST-πare correlated with tumor histological types, tumor histological type may be a important index which can appraise chemotherapy multidrug resistance.(3)In gastric cancer, the expression of HIF-1αare correlated with tumor invasion depth and lymph nodes metastasis, HIF-1αmay promote tumour invading and metastasis ability by some inherent mechanism.(4)The more serious anemia may cause hypoxia of tumor microenvironment and then stronger multidrug resistance, then increase the expression of P-gp, GST-π, and decrease the expression of TOPO-Ⅱ; the expression of P-gp, HIF-1αin gastric cancer and Hb concentration is positive correlation with each other, suggests that, HIF-1αmay be one of the inducible factors in the process.