The Expression And Significance Of FGF2?FGFR2?p-ERK1/2 In Idiopathic Pulmonary Fibrosis And Non-small Cell Lung Cancer

The idiopathic pulmonary fibrosis(IPF)is a kind of unexplained chronic diffuse interstitial lung disease.The primary bronchopulmonary carcinoma,which is originated from the bronchial mucosa or glands,is the most common in primary lung malignant tumors.The primary bronchopulmonary carcinoma is divided into two categories,namely,small cell lung cancer and non-small cell lung cancer.The studies have shown that IPF,and NSCLC have an obvious correlation in gene mutation,epigenetics,the activation of specific signaling pathways and the abnormal expression of micro RNAs.Besides,in clinical,the IPF and lung cancer both response to treatments poorly and have bad prognosis.In recent studies,it has been proved that the patients of IPF combined with lung cancer have a poorer prognosis and a lower survival rate.The tyrosine kinase pathway which is the important signaling pathway is strongly activated not only in many cancers but also in IPF.The tyrosine kinase receptors contain vascular endothelial growth factor receptor(VEGFR),fibroblast growth factor receptor(FGFR)and platelet-derived growth factor receptor(PDGFR).The pathway once activated will regulate cell growth,differentiation,adhesion,motility,apoptosis and other important physiological processes,which are associated with the initiation or progression of cancer.In this study,we focused our research on the expression of FGF2/FGFR2,and the downstream ERK1/2/p-ERK1/2 in NSCLC patients,IPF patients and other nonmalignant diseases patients to verify the common pathogenesis between the IPF and NSCLC.The correlation between the expression of FGF2,FGFR2 and p-ERK1/2 in NSCLC patients and the related clinical factors(gender,age,smoking history,lymph node metastasis,clinical stage and histological type)were also analysed in the study.This study will lay theoretical foundations for basic research and clinical research about the IPF and lung cancer.Methods:Quantitative reverse transcription-polymerase chain reaction(RT-q PCR)and western blot were used to detect the expression of FGF2,FGFR2,ERK1/2 and p-ERK1/2 in carcinoma tissue and para-carcinoma tissue in NSCLC patients,bronchoalveolar lavage fluid in the IPF patients and the normal control group.The normal control group refers to the patients with the main sympotom of cough and confirmed healthy by the bronchoalveolar lavage.Results:(1)Compared with the para-carcinoma tissue,the FGF2 m RNA and protein expression in lung carcinoma tissue are significantly increased(P<0.001).Compared with the control group,the FGF2 protein expression in IPF patients' bronchoalveolar lavage fluid is increased(P=0.009).There is no correlation between the expression of FGF2 protein and the sex,age,smoking history and histological type of the NSCLC patients.However there is a significant difference of FGF2 protein in patients with and without lymph node metastasis(P=0.013).The difference is obvious in patients of different clinical stage(P=0.03).The expression of FGF2 protein is positively correlated with the lymph node metastasis and the clinical stage.(2)Compared with the para-carcinoma tissue,the FGFR2 b m RNA expression is significantly decreased(P<0.001)and the FGFR2 c m RNA expression is significantly increased(P<0.001)in lung carcinoma tissue.Compared with the para-carcinoma tissue,the FGFR2 c protein expression in lung carcinoma tissue is significantly increased(P<0.001).Compared with the control group,the expression of FGFR2 protein in IPF patients' bronchoalveolar lavage fluid is increased(P=0.027).There is no correlation between the expression of FGFR2 c protein and the sex,age,smoking history and histological type of the NSCLC patients.However there is a significant difference of FGFR2 c protein in patients with and without lymph node metastasis(P=0.007).The difference is obvious in patients of different clinical stage(P=0.034).The expression of FGFR2 c protein is positively correlated with the lymph node metastasis and the clinical stage.(3)Compared with the para-carcinoma tissue,the ERK1/2m RNA expression is significantly increased(P<0.001)in lung carcinoma tissue.However,there is no significant difference in the expression of ERK1/2 protein of lung carcinoma tissue and para-carcinoma tissue(P=0.251).Compared with the para-carcinoma tissue,the p-ERK1/2 protein expression in lung carcinoma tissue is significantly increased(P<0.001).Compared with the control group,the p-ERK1/2 protein expression in IPF patients' bronchoalveolar lavage fluid is increased(P=0.001).There is no correlation between the expression of p-ERK1/2 protein and the sex,age,smoking history,histological type,lymph node metastasis and clinical stage of the NSCLC patients.Conclusion:(1)The expression of FGF2,FGFR2 and p-ERK1/2 protein in NSCLC patients and IPF patients is increased than the control group.The increased expression of FGF2/FGFR2/p-ERK1/2 suggests that the signaling pathway may contribute to the pathogenesis of lung fibrosis in IPF patients and tumorigenesis in NSCLC patients.(2)The protein expression of FGF2 and FGFR2 c is positively correlated with the lymph node metastasis and the clinical stage,which suggest s the upregulated FGF2 and FGFR2 c protein might be involved in the invasion,metastasis and prognosis of NSCLC.