Expression And Clinicopathologic Significance Of Ago2 In Adenocarcinoma Patients With EGFR Gene Mutation

Objective:We assessed Ago2 and hypoxia-inducible factor 1alpha(HIF1α) protein expression in lung adenocarcinoma patients with the mutant and wild type of EGFR with immunohistochemistry(IHC), discussed about the relation of Ago2 with clinicopathological data and the EGFR status under the hypoxic stress, then further analyzed the role of combined detection of Ago2, HIF1α and the EGFR status in predicting the oncogenesis, invasion and metastasis of lung adenocarcinoma.In this way, We hope we could provide a new sight into the diagnose, therapy and prognosis of lung adenocarcinoma.Methods:The human lung adenocarcinoma specimens were collected from 160 primary lung adenocarcinoma patients, including 40 surgically excised specimens, 40 bronchoscopy biopsy specimens and 40 pleural effusion specimens. In all specimens, Ago2 and HIF1αprotein expression were assessed with immunohistochemistry, while EGFR mutation is identified by direct DNA sequencing of polymerase chain reaction-amplified regions of exons 19 and 21.Results:1. The relationship between the EGFR gene mutation and clinicopathological features of adenocarcinoma: EGFR mutation is found in 45 patients of the all 160 patients(28.1%), including 24 patients with mutation in exon 19(24/45,53.3%) and 21 patientswith mutation exon 2 l. The constituent ratio of mutation in female(26/66,39.4%)is respectively higher than male(19/94, 20.2%), P=0.008. Between never smokers and smokers,the constituent ratio of mutation is 64.4% and 35.6%( P=0.001), respectively. 2.The relationship between the Ago2 and clinicopathological features of adenocarcinoma:Ago2 expression levels in lung adenocarcinoma samples were significantly down-regulated compared with healthy controls(P<0.001), in addition, there is a significant difference between the EGFR mutant and wild-type cases that Ago2 protein overexpressed in the EGFR mutant cases respectively(P<0.001), which has relations with gender(P=0.015) and smoking history(P=0.033) and no relations with age and the EGFR mutantion types(P>0.05). 3. The relations with the expression of Ago2 and HIF1α: The expression level of Ago2 was negatively correlated with that of HIF1α both in lung adenocarcinoma patients with the mutant(r=-0.428, P=0.003) and wild type of EGFR(r=-0.208,P=0.025)Conclusions:Ago2 expression levels in lung adenocarcinoma samples were significantly reduced compared with healthy controls, and the expression intensity is related with the EGFR status, gender and smoking history while has no relations with age and the EGFR mutantion types. The expression level of Ago2 was negatively correlated with that of HIF1α both in lung adenocarcinoma patients with the mutant and wild type of EGFR. Thus,as a new biomarker, Ago2 could be involed the occurrence, development, and metastasi of lung adenocarcinoma by the interaction with EGFR under the hypoxic stress. These findings may shed light on a potential strategy of the diagnose, therapy and prognosis in lung adenocarcinoma.