Correlation Of PI3K-Akt Pathway And Prognosis Of Lung Cancer Patients

Background Lung cancer is the most common primary pulmonary malignant tumors; it has been a serious threat to human health and life. PI3K-Akt pathway is closely associated with non-small cell lung cancer. Currently, we made some progress against lung adenocarcinoma with EGFR-TKI treatment, and PI3K-Akt pathway is considered to be most closely related to EGFR-TKI. High expression of PI3K-Akt was found in resistant cell line. Till now, there is little research about patients with lung adenocarcinoma dealt with EGFR-TKIs after surgery.Objective To investigate the expression of PI3K/AKT in primary lung cancer lesions, and the relation with sensitivity of EGFR-TKIs in patients with lung adenocarcinoma.Methods This study included356cases of patients that receiving radical surgery for lung adenocarcinoma in Peking Union Medical College Hospital within2001-2011. Follow-up to257, with99lost. After reading the clinical medical records, we integrated follow-up and clinical data. On the other hand, in the follow-up to257cases, there are fresh lung cancer tissue samples in99cases (both adjacent tissues in part of them). The Western Blot of PI3K p-85and p-Akt was used, to detect protein expression. Further analysis the relations between EGFR mutations in lung adenocarcinoma patients, the expression of PI3K p-85and p-Akt and the Clinical information factors, for sensitivity and prognosis analysis. To find the meaning of taking EGFR-TKIs in those patients that receiving radical surgery for lung adenocarcinoma, and the relations between PI3K-Akt expression and the sensitivity of EGFR-TKIs.Results This experiment has a follow-up to257patients, including95cases with EGFR mutation positive, Accounting for59.0%. A slightly higher proportion of the mutation in females was found,χ2=0.374, P=0.541. And higher mutation rate was discovered in the non-smoking group than smoking group,χ2=6.126, P=0.013. The analysis of257cases with different stages found that, the median PFS in the Stage Ⅰ>10years, median OS>10years; the median PFS in the Stage Ⅱ=3.9years, median OS>8.3years; the median PFS in the Stage Ⅲ=1.3years, median OS>3.9years; and the median OS in the Stage Ⅳ=2.9years. The Western Blot of PI3K p-85and p-Akt showed that higher expression of these2protein in adjacent tissues than in lung adenocarcinoma tissues, with a certain degree of statistical significance (P=0.003, P=0.068). There is a certain correlation between the expression levels of two proteins (P=0.048), However, the expression of two proteins and EGFR mutations had no significant association. Within the follow-upped257patients,77of them received EGFR-TKI therapy; we did not find statistically significant improvement in those who were dealt with TKIs before disease progression; but seems to have some effect in those who were dealt with TKIs after disease progression(only in Stage III, P=0.030). In this experiment, no statistically significant results were found in the study of EGFR-TKI sensitivity and resistance for those who eceived EGFR-TKI therapy after surgery for lung adenocarcinoma.Conclusion In this experiment, female, non-smoking group, as well as a higher degree of differentiation of lung adenocarcinoma patients showed higher EGFR mutation rate. Patients with higher installments showed a lower PFS and OS. PI3K p-85and p-Akt showed a higher expression of these2protein in adjacent tissues than in lung adenocarcinoma tissues, and a certain correlation between the expression levels of these two proteins, However, the expression of these two proteins and EGFR mutations had no significant association. EGFR-TKIs therapy seemed to have a role in prolonging PFS and OS of the patients after surgery for lung adenocarcinoma. No statistically significant results were found in the study of EGFR-TKI sensitivity and resistance for those who received EGFR-TKI therapy after surgery. In further research, a prospective study, strict inclusion criteria and confirming mechanism, Longer follow-up time limit, and A larger experimental study sample size, were needed to produce more meaningful results.