| Objective In this study,the expression of HIF-1α,P-gp and COX-2 are detected in 60 cases of non-small cell lung cancer tissues specimens and 30 cases of adjacent normal lung tissues specimens , in order to analyze the relationship between their expression and the clinicopathological features of patients with NSCLC including age, gender, smoking history, lung cancer pathological type, tumor size, lymph node metastasis, clinical stage and prognosis. To explore the correlation among them .To provide some guidance for non-small cell lung cancer diagnosis, assessment, treatment and prognosisMethods To Collect non-small cell lung cancer after surgical resection specimens of 60 cases, adjacent normal lung tissue (from cancer≥5cm in a normal lung tissue) of 30 cases in January 2003 ~ December 2005 in Ningxia Medical University Affiliated Hospital. All cases are stained through HE to make joint pathology by three experienced pathologists. There are a complete clinical case information in 60 cases of patients and follow-up patients in 3 years, 5-year survival. Using Immunohistochemical staining to detect P-gp and COX-2, in situ nucleic acid hybridization to detect HIF-1αin 60 cases of NSCLC tumor tissues and 30 adjacent normal lung tissues. All experimental data statistical analyses are carried out with using SPSS13.0 statistical analysis software. All of the statistical tests are two-sided and P values of 0.05 or less are considered to be statistically significant.Results 1. P-gp in non-small cell lung cancer tissues by immunohistochemistry results: P-gp positive expression is mainly located in non-small cell lung cancer cell cytoplasm and membrane. Lung cancer P-gp expression-positive rate of 56.7 percent (34/60), normal lung tissue expressed as 10.0 percent (3/30). Two groups between lung cancer tissues and adjacent normal lung tissue are statistically significant (P<0.05). In 60 patients with non-small cell lung cancer tissue samples, P-gp expression is not associated with gender, age, tumor location (P>0.05), and associated with TNM staging, pathological grade (P<0.05). P-gp in primary tumor≥5cm, lymph node-positive, clinical stagingⅢperiod of non-small cell lung cancer expressed clear high, Two groups are statistically significant (P<0.05). P-gp in low differentiation cancer rate is significantly higher than well-differentiated. Two groups are statistically significant (P<0.05). The 3,5year survival rate of P-gp positive expression is significantly lower than P-gp negative group. By chi-square test, the difference is significant (P<0.05). 2. COX-2 in non-small cell lung cancer tissue immunohistochemical results: COX-2 positive expression is mainly located in non-small cell lung cancer cell cytoplasm. Lung cancer COX-2 expression-positive rate of 63.33 percent (38/60), normal lung tissue expressed as 6.67 percent (2/30). Two groups between lung cancer tissues and adjacent normal lung tissue are statistically significant (P<0.05). In 60 patients with non-small cell lung cancer tissue samples, COX-2 expression is not associated with gender, age, tumor location (P>0.05), and associated with TNM staging, pathological grade (P<0.05). COX-2 in primary tumor≥5cm, lymph node-positive, clinical stagingⅢperiod of non-small cell lung cancer expressed clear high, Two groups are statistically significant (P<0.05). COX-2 expression in lung cancer pathology type adenocarcinoma, squamous cell carcinoma expressed are the 88.24%, 55.88%, Two groups are statistically significant (P<0.05). COX-2 in low differentiation cancer rate is significantly higher than well-differentiated. Two groups are statistically significant (P<0.05). The 3,5year survival rate of COX-2 positive expression is significantly lower than COX-2 negative group. By chi-square test, the difference is significant (P<0.05). 3. HIF-1αin non-small cell lung cancer tissues in situ nucleic acid hybridization results. HIF-1αpositive expression is mainly located in non-small cell lung cancer cell cytoplasm. Lung cancer HIF-1αexpression-positive rate of 45.0 percent (27/60), normal lung tissue expressed as 6.67 percent (2/30). Two groups between lung cancer tissues and adjacent normal lung tissue are statistically significant (P<0.05). In 60 patients with non-small cell lung cancer tissue samples, HIF-1αexpression is not associated with gender, age, tumor location (P>0.05), and associated with TNM staging, pathological grade (P<0.05). HIF-1αin primary tumor≥5cm, lymph node-positive, clinical stagingⅢperiod of non-small cell lung cancer expressed clear high, Two groups are statistically significant (P<0.05). HIF-1αin low differentiation cancer rate is significantly higher than well-differentiated. Two groups are statistically significant (P<0.05). The 3,5year survival rate of HIF-1αpositive expression is significantly lower than HIF-1αnegative group. By chi-square test, the difference is significant (P<0.05). 4. The correlation of HIF-1α, P-gp, COX-2 expression in non-small cell lung cancer : Using Spearman correlation test to analyze the correlation among HIF-1α, P-gp and COX-2 expression in NSCLC tissue. P-gp and HIF-1α,P-gp and COX-2 ,HIF-1αand COX-2 expression in NSCLC tissues showed positive correlation. There are statistically significant (P<0.05). 5. Kaplan-Meier survival analysis: Single-factor analysis of non-small cell lung cancer HIF-1α, P-gp, COX-2 expression on the prognosis, the results show that HIF-1α, P-gp, COX-2 three negative survival rate higher than the positive survival rate . There are statistically significant (P<0.05). 6. COX proportional hazard regression analysis: COX proportional hazard analysis indicates that multiple factors HIF-1α, P-gp, COX-2 overexpression , tumor size, TNM, differentiation and lymph node metastasis are important factors for the survival time of patients (P<0.05). While the gender, age, tumor sites and operations way are no obvious influence for the survival time of patients (P>0.05). Conclusion 1 This study showed that: 1.The expression of HIF-1α, P-gp, COX-2 is existed in non-small cell lung cancer. The expression in tumor tissues was significantly higher than in adjacent normal lung tissue. 2. The expression of HIF-1α, P-gp, COX-2 in non-small cell lung cancer expression is not associated with gender, age, tumor location, but positively correlated with tumor size, cell differentiation, clinical stage, lymph node metastasis. The study shows that HIF-1α, P-gp, COX-2 participated in non-small cell lung cancer development, and can be used as an assessment indicator of poor prognosis of lung cancer. 3. HIF-1α, P-gp, COX-2 has a high correlation among them. This indicates a number of gene synergies may exist in HIF-1α, P-gp, COX-2. To explore the possibility of providing clues by regulating HIF-1α, COX-2 inhibitor to reverse tumor drug resistance. To look for more ways to improve non-small cell lung cancer prognosis .
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