Expressions Of Insulin-like Growth Factor Receptor-1(IGF1R) And Cezanne-1 In Lung Adenocarcinoma

Backgrounds And Objectives:Lung cancer is one of the leading causes of cancer-related deaths.In 2012,lung cancer accounts for 13%of new total cancer cases and adds a heavy burden on society.Exploring the mechanism of development and finding the potential targets for treatment are important for the lung cancer.Once binded with ligands,the intracellular kinase will be activated through an autophosphorylation-induced conformational change and so will the downstream signalling cascades,including two major downstream signaling pathways,the phosphoinositide 3-kinase(PI3K)-Akt pathway and the Shc-Ras-MAPK pathway.And ultimately it leads to major biological outcomes such as tumor transformation,maintenance of tumorigenicity,promotion of cell growth,and prevention of apoptosis.The modification of ubiquitination and endocytosis were considered critical in the termination of the signal.Cezanne-1,known as a new type of deubiquitinating enzymes(DUBs),was considered to be associated with enhancement of EGFR signaling pathway and reduced degeneration of EGFR.The purpose of this study is to discuss the possibility of cezanne-1 as a deubiquitinating enzyme for IGF1R and predictive significance of IGFIR and cezanne-1 for patients with lung adenocarcinoma.Methods:We used data in R2 system to initially prove the correlation between cezanne-1 and IGF1R and study their predictive significance.Cezanne-1 and IGF1R expression were evaluated in 103 patients with lung adenocarcinoma using immunohistochemical(IHC)analysis.The relationship between expression of cezanne-1 and IGF1R was analyzed by ?2 test.Whether clinical variables have prognostic significance were estimated by Cox regression analyses.Kaplan-Meier method was used to generate the survival curve and the significance of difference was calculated by log-rank test.The relationship between expression of cezanne-1 and IGF1R was also analyzed by ?2 test.Results:R2 system analysis showed positive IGF1R expression was significantly associated with poor prognosis of NSCLC patients.Besides,cezanne expression was significantly associated with IGF1R expression.The expressions of IGF1R and cezanne were higher in tumors than in normal tissues.Expression of cezanne-1 was significantly associated with lymph node metastasis(p = 0.004)and pathological stage(p = 0.040).Univariate analysis revealed that cezanne-1 expression(HR=6.024,p<0.001),IGF1R expression(HR 3.616,p=0.001),tumor size(HR 2.774,p=0.002),lymph node metastasis(HR 3.059,p=0.001)and differential degree(HR 7.430,p=0.006)were significantly associated with overall survival(Table 3).Multivariate analysis confirmed that cezanne-1 expression and IGF1R expression were independent prognostic factors for overall survival.There was a significant association between cezanne-1 and IGF1R(x2,20.063 p<0.001).Conclusion:Our findings indicate both cezanne-1 expression and IGF1R were negative independent predictive factors for the prognosis of lung adenocarcinoma respectively.There was a close interrelationship between cezanne-1 expression and IGF1R expression.