The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis

Abstract

Jieer Ying,1,2 Qi Xu,2 Bixia Liu,2 Gu Zhang,3 Lei Chen,2 Hongming Pan11Department of Chemotherapy, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 2Department of Chemotherapy, 3Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaObjective: To analyze the correlation between sequential aspects of the phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by immunohistochemistry in the primary lesion of gastric cancer, clinicopathologic factors, and survival in Chinese patients to explore the role of sequential analysis of multiple targets in prognoses.Methods: Immunohistochemistry was performed to examine the expression of PI3K, phosphorylated-AKT (p-AKT), and phosphorylated-mTOR (p-mTOR) in 59 primary lesion samples ranging from Stages I to IV after gastrectomy. The correlation between sequential expression of multiple targets, and clinicopathologic factors and survival was analyzed.Results: The positive expression rates of PI3K, p-AKT, and p-mTOR were 49%, 58%, and 56%, respectively. There were eleven cases with three biomarkers positive (19%), 22 cases with two biomarkers positive (37%), and 19 cases with only one biomarker positive (32%). Seven cases (12%) were all negative. Multi-factorial Cox regression analysis showed that neural invasion, vascular invasion, size of the tumor, lymph nodes affected, metastasis, carbohydrate antigen 19-9 level, and PI3K/p-AKT/p-mTOR simultaneous expression were independent prognostic parameters. The risk of death for the cases with two biomarkers positive was 0.367 times that for the cases with three biomarkers positive (P=0.166). The risk of death for the cases with only one biomarker positive was 0.105 times that for the cases with three biomarkers positive (P=0.058). The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022).Conclusion: Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome. But we need more rigorous validation in a larger data set. Keywords: gastric cancer, PI3K/AKT/mTOR, prognosis