Differential Analysis Of Expression Of VEGF-A,VEGFR-2 And DLL4 In Different Pathological Types Of Lung Cancer

Background :Lung cancer is a malignant tumor originating from the bronchial mucosa or gland.Smoking and air pollution have made the incidence of lung cancer rising year by year.With the continuous improvement of the medical level,the treatment of lung cancer has also been treated with radiotherapy,chemotherapy,and targeted drug therapy.In the target therapy,"anti-angiogenesis" is the hot spot of recent research.Because the growth and metastasis of lung cancer require rich blood vessels to provide sufficient oxygen and nutrients.Therefore,tumor tissue can secrete many kinds of angiogenic substances,and induce and regulate angiogenesis through multiple pathways of vascular signaling transduction and interaction.There are two main pathways of angiogenic signaling pathway found at present.The one signaling pathway is VEGF(vascular endothelial growth factor)/VEGFR(vascular endothelial growth factor receptor),which is currently on the pathway of most,and achieved remarkable results.Targeted drugs of VEGF/VEGFR pathway such as bevacizumab has been clinically proven in combination with chemotherapy for first-line and second line non squamous cell carcinoma patients with advanced non-small cell lung cancer,which has been recommended by the international tumor guide NCCN(National Comprehensive Cancer Network).The VEGF family is divided into VEGF-A,VEGF-B,VEGF-C,VEGF-D and so on,and the biological regulation activity of VEGF-A is the most important.The most commonly known VEGF is VEGF-A.In the VEGF receptor,the VEGFR-2 signaling pathway is the most critical.So we choose VEGF-A and VEGFR-2to reflect the overall level in the study.The single inhibition of VEGF-VEGFR isobviously far from enough.Therefore,it is necessary to further explore the other vascular signaling pathways as a therapeutic target.The other signal pathway is DLL4(delta-like ligand 4)/Notch.The DLL4/Notch pathway regulates angiogenesis by regulating the differentiation of the arteriovenous and the induction and selection of the induced tip cells of the tip cells.In normal physiological conditions,DLL4 is specifically expressed in the vascular system,such as the developing embryo,the neovascularization,and so on.At present,some related studies have shown that the expression of DLL4 in a variety of malignant tumors,such as liver cancer,colon cancer,breast cancer and so on.In animal experiments,it was found that inhibiting the expression of DLL4 can lead to overgrowth and malfunction of blood vessels,and prevent the supply of tumor nutrients,but it can delay the progression of tumors.Therefore,it has been expected to be a new target for the prevention and treatment of lung cancer.Objective: To investigate the differences and correlations between vascular endothelial growth factor-A(VEGF-A),vascular endothelial growth factor receptor-2(VEGFR-2)and Delta like ligand 4(DLL4)expression in different pathological types of lung cancer.It provides new targets for the treatment of lung cancer.Methods: The pathological specimen came from lung cancer patients who were first treated by surgical operation in Qingdao municipal hospital from 2009 to2017.They were diagnosed by pathology and immunology.A total of 110 cases were divided by gender: 75 males and 35 females.The maximum age of 87 years,the lowest29 years,the average age of 59 years.Among them: small cell lung cancer: 40 cases;squamous cell carcinoma: 35 cases;adenocarcinoma: 35 cases.At the same time,20 normal tissues adjacent to the cancer 2cm were selected as the control group.Immunohistochemistry was used to detect the expression level of VEGF-A,VEGFR-2and Dll4 protein in the tissues.The differences between the three expression in small cell lung cancer,non-small cell lung cancer and adjacent normal tissues were analyzed in turn.In addition,we compared the expression levels of three in non-small cell lung cancer with gender,age,pathological type,differentiation degree,lymph nodemetastasis and TNM stage.Finally,the correlations between the three VEGF-A,VEGFR-2 and DLL4 was analyzed.Results: 1.the positive rates of VEGF-A,VEGFR-2 and DLL4 in non-small cell lung cancer and small cell lung cancer were significantly higher than those of normal tissues adjacent to cancer(P<0.01).2.The expressions of VEGF-A,VEGFR-2 and DLL4 in non-small cell lung cancer and small cell lung cancer are not statistically significant(P>0.05).3.The expressions of VEGF-A,VEGFR-2 and DLL4 in non-small cell was correlated with differentiation,lymph node metastasis and TNM stage(P<0.05).But not significantly different from gender,age and pathological type(P>0.05),4.Both in small cell lung cancer and non small cell lung cancer,the expressions of the three have a highly positive correlation(P<0.01).Conclusion: DLL4/Notch signaling pathway has potential to become a new target for lung cancer treatment.VEGF/VEGFR is also promising in small cell lung cancer.The combination of two angiogenesis drugs may inhibit tumor growth better.Antiangiogenic drugs may be effective in advanced lung cancer with high degree of differentiation and lymph node metastasis.