Expression Of AKT And P-AKT Protein And Its Correlation With PD-L1 Protein And Clinical Significance In Lung Adenocarcinoma

Objective:Dysregulation of PI3K/AKT/mTOR signaling pathway has an important effect in the formation and development of lung adenocarcinoma.Previous study suggested that the activation of PI3K/AKT/mTOR signaling pathway is linked to the expression of tumor programmed death ligand-1(PD-L1),but it remains controversial.In the current study,we investigated the expression of AKT and p-AKT and its relationship with clinicopathological features,analyzed the factors affecting lung adenocarcinoma prognosis,and explored the relationship between AKT,p-AKT and PD-L1.Methods:The expression of AKT,p-AKT and PD-L1 protein in 110 cases lung adenocarcinoma tissues were established by immunohistochemical staining.The correlation between AKT,p-AKT and clinicopathological features were compared by chi-square test and FISH exact test.Spearman rank correlation method was used to analyze the correlation between AKT,p-AKT and PD-L1 protein.Kaplan-Meier and Log-rank test were used to analyze the relationship between the different groups.The COX regression model was used to analyze the multivariate analysis.P values of<0.05 were considered to be statistically significant.Results:AKT and p-AKT were mainly expressed in the cytoplasm and less commonly in the nucleus.The positive rate of AKT and p-AKT was 64.5%(71/110)and 44.5%(49/110),and was related to EGFR mutant(p=0.016,p=0.014,respectively),irrespective of age,gender,smoking status,TNM stage,degree of differentiation or lymph node metastasis(p > 0.05).The positive rate of PD-L1 was 38.2%(42/110).No correlation was found for AKT and PD-L1 protein(r=0.036,p=0.387).Negative correlation trend was discovered for p-AKT and PD-L1 protein(r=0.162,p=0.063).The expression of AKT and p-AKT was not associated with 3-year disease free survival rate and 3-year overall survival rate(p>0.05).TNM stage(p=0.014)was an independent risk factor for recurrence/metastasis in patients with lung adenocarcinoma after surgery.Recurrence type(p=0.000)was an independent risk factor for the 3-year survival rate in patients with postoperative lung adenocarcinoma.Conclusion:The activation of the PI3K/AKT/mTOR signaling pathway existed inlung adenocarcinoma tissues,and was associated with EGFR gene mutation.There was a negative correlation trend between p-AKT and PD-L1,suggesting that PI3K/AKT/mTOR in the downstream pathway of EGFR may negatively regulate the expression of PD-L1.The expression of AKT and p-AKT had no impact on the prognosis of lung adenocarcinoma.TNM stage was an independent predictor of tumor recurrence/metastasis and tumor recurrence type was an independent prognostic factor for overall survival in patients with postoperative lung adenocarcinoma.