Research On The Reationship Between Expressions Of NOK And FGFR2and Proliferation Of Non-small Cell Lung Cancer

BackgroundLung cancer incidence is increasing in current years.Lung cancer is also the firstcancer death in the worldwide, in which80%to90%of patients is non-small cell lungcancer (NSCLC). The five-year survival rate of patients with lung cancer is still low,although many treatments have been improved.Receptor protein tyrosine kinases（RPTKs,Receptor protein tyrosine kinases）play asignificant important role in the adjustment of tumor cell apoptosis, proliferation,migration and other processes.The new proto-oncogene NOK（Novel Oncogene withKinase-domain） with kinase domain structure is a recently discovered oncogene. NOKand the fibroblast growth factor receptor (FGFR2) belong to the family of receptor protein tyrosine kinase, and they have30%homology. Ki67can reflect the cell proliferationeffectively, and it is the most widely used marker of cell proliferation.Studies have shownthat NOK and FGFR2were associated with cancer invasion and metastasis, but theexpressions and biological characteristics in lung cancer are still unknow. At the same time,NOK and FGFR2effects on tumor proliferation issues remain to be further researched.ObjectiveTo detect the expressions and locations of NOK and FGFR2protein and identify thecorrelation of NOK and FGFR2in NSCLC, and to confirm the effect of NOK and FGFR2for NSCLC proliferation.Methods1The expressions of NOK and FGFR2protein were detected byimmunohistochemical method in163NSCLC tumor samples and the correlation wasanalyzed by statistical software.2The co-localization of NOK with FGFR2in NSCLC was detected by laser confocalmicroscopy.3The expressions of FGFR2in52NSCLC tissue and normal tissue were detected byRT-pcr and western blot, and the differences between NSCLC tissue and normal tissue wasanalyzed by statistical software.4The expressions of Ki67protein were detected by immunohistochemical method in163NSCLC tumor samples, the correlations of NOK,FGFR2and Ki67were anlalyzed bystatistical software.Results1Immunohistochemical results showed that the expressions of NOK and FGFR2protein in different TNM stages and pathological grades were different statistically（P＜0.05）. The correlation between NOK and FGFR2expression was found in total NSCLCsamples, squamous cell carcinoma and adenocarcinoma were highlysignificant,P=0.000,the correlation coefficient rswere0.640,0.684,0.597, respectively.2The laser confocal microscope result showed that the expressions of NOK andFGFR2exist co-localization phenomenon.NOK mainly express in cytoplasm, FGFR2 mainly express in cytoplasm and cytomembrane.3RT-PCR results showed that: the expressions of FGFR2in NSCLC were higherthan normal lung tissue（P＜0.05）, the expressions of FGFR2protein at differentpathological grades and different TNM stages were various statistically（P＜0.05）.Western blot result showed that: the expressions of FGFR2in NSCLC were higher thannormal lung tissue（P＜0.05）. The results are consistent with immunohistochemicalresults.4Immunohistochemical results showed that: the correlation between NOK and Ki67was found in NSCLC samples, squamous cell carcinoma samples and adenocarcinomasamples were highly significant, P=0.000,the correlation coefficient rswere0.523,0.463,0.580, respectively. The correlation between FGFR2and Ki67expression was found inwhole NSCLC samples, squamous cell carcinoma and adenocarcinoma were highlysignificant, P=0.000,the correlation coefficient rswere0.417,0.424,0.425, respectively.Conclusions1The expressions of NOK and FGFR2protein are associated with the malignantdegree of NSCLC, NOK and FGFR2protein are highly expressed in low differentiation ofNSCLC, which indicates that the two may be associated with NSCLC tumorproliferation.The expressions of NOK and FGFR2protein at different TNM stagesindicate that the both may be associated with NSCLC migration, invasion ability. Thecorrelation of the expressions suggest that there may be interactions between NOK andFGFR2.2The expressions of NOK and FGFR2exist co-localization and correlation inNSCLC, and they are located in cytoplasm. These results indicate that there may beinteraction between NOK and FGFR2, and provide evidence for further study.3RT-PCR and western blot results showed that the expression of FGFR2wasassociated with the proliferation,migration and invasion in NSCLC, which indicated thatFGFR2could affect the tumorigenesis and development of NSCLC.4NOK and FGFR2showed a positive correlation with Ki67in NSCLC, whichmay be associated with NSCLC proliferation, the specific mechanisms would be further proved.