Significance Of VEGF,HIF-1α,COX-2 Alone Expression And In Combination In Advanced Non-small Cell Lung Cancer

Objective: Advanced lung cancer is prone to construct hypoxic microenvironment,activate hypoxia inducible factor-1α and induce downstream target genes vascular endothelial growth factor and cyclooxygenase-2,stimulating tumor angiogenesis,invasion and immune suppression.Three factors are closely related,and their high expression in the course of tumor development is often closely associated with the poor prognosis of patients.In this experiment,we test the expression level of VEGF,HIF-1α and COX-2 in peripheral serum and pleural effusion of advanced non-small cell lung cancer,and analyze the correlation of VEGF,HIF-1α and COX-2 alone and the clinicopathological characteristics of advanced non-small cell lung cancer,providing a theoretical basis for new potential targets of non-small cell lung cancer.Methods: 100 non-small cell lung cancer patients were admitted to Taizhou People’s Hospital from December 2021 to December 2022,including 33 patients as squamous cell carcinoma group and 67 patients as adenocarcinoma group,and 30 healthy examination patients were selected as normal control group.A total of 28 patients in the 100 non-small cell lung cancer patients had pleural effusion as the malignant pleural effusion group,and 15 patients with inflammatory pleural effusion were selected as the control group of benign pleural effusion.Clinical data of all study subjects were collected,and making ELISA experiment to determine the expression of VEGF,HIF-1α,and COX-2 with clinicopathological characteristics,Glass score,and ECOG PS score of advanced nonsmall cell lung cancer.Statistical analysis was performed with SPSS 26.0,mean ± standard deviation was used in the measurement data;T test was used for comparison between two groups;rank sum test was used for two-sample comparison.Count data were expressed by percentage or percentage,and comparisons between two groups were performed by χ 2 test or Fisher’s exact probability test.For the correlation analysis of two or more continuous non-normal variables,the Spearman correlation analysis was used.Statistical significance was considered as a difference of p<0.05.Result: The result of this study shows that:1.In the total population of non-small cell lung cancer,the expression level of VEGF is closely correlated with tumor size and tumor differentiation(93.8% vs.78.4%,100% vs.82%)(P <0.05);VEGF,HIF-1α,COX-2 is closely correlated to lymph node metastasis(93.0% vs.69.0%,80.2% vs.44.8%,97.2% vs.79.3%)(P <0.05);2.Serum VEGF,HIF-1α and COX-2 are significantly higher in lung squamous cell carcinoma and adenocarcinoma groups(90.9% 、 73.6% vs.10%,48.4% 、 80.5% vs.3.3%,87.8%、94.6% vs.20%)(P <0.05);The expression of HIF-1α is different in the pathological types of squamous adenocarcinoma,and the expression level of lung adenocarcinoma group is significantly higher than that of squamous cell carcinoma group and control group(80.5%,48.4% vs.3.3%)(P <0.05);3.In the total population of non-small cell lung cancer,The combined expression of VEGF,HIF-1α and COX-2 is significantly associated with lymph node metastasis status and degree of tumor differentiation and PS score(73.2% vs.31.0%,81.8% vs.55.1%,92.3% vs.56.3%)(P <0.01)(P <0.05)(P <0.05);The combined expression of VEGF and HIF-1α is significantly associated with the degree of tumor differentiation and PS score(86.4% vs.55.1%,92.3% vs.57.4%)(P <0.01)(P <0.05);4.Using the rank sum test for the positive expression data of the three groups shows that the combined expression of VEGF,HIF-1α and COX-2 is closely related to Glasgow score,statistically significant(P <0.05);5.In the pleural effusion,the positive expression level of VEGF,HIF-1α are significantly higher in malignant than benign(92.8% vs.13.3%,82.1% vs.20%)(P <0.01);However,the positive expression of VEGF and HIF-1α is more significantly different in benign and malignant pleural effusions(P <0.01),Higher specificity of VEGF,HIF-1α alone(93.3% vs.86.7%、80.0%)(P <0.01).Conclusion: 1.The expression of HIF-1α in the pathological types of squamous cell adenocarcinoma is different,and the positive expression level of lung adenocarcinoma group is significantly higher than that of squamous cell carcinoma group and control group.2.The expression of VEGF is correlated with tumor size and degree of tumor differentiation in intermediate and advanced non-small cell lung cancer.3.The combined expression of VEGF,HIF-1α and COX-2 is significantly correlated with the lymph node metastasis status and the degree of tumor differentiation and PS score of advanced non-small cell lung cancer;the combined expression of VEGF and HIF-1α is closely correlated with the degree of tumor differentiation and PS score of advanced non-small-cell lung cancer.4.The combined positive expression of VEGF,HIF-1α and COX-2 is correlated with the Glasgow score before the treatment of advanced non-small cell lung cancer.5.In the unexplained pleural effusion,VEGF combined with HIF-1α can more effectively predict the properties of the pleural effusion.6.The result of this study shows that targeted inhibition of VEGF / HIF-1α / COX-2 signaling pathway may be a potential future research hot spot for advanced non-small cell lung cancer.