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

Abstract

Objective

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

Acknowledgments

This work was supported by the Natural Scientific Foundation of Zhejiang Province, People’s Republic of China (LY14H160008).

Author contributions

Hongming Pan was responsible for substantial contributions to conception and design. Qi Xu was responsible for acquisition of data, or analysis and interpretation of data. Jieer Ying was responsible for drafting the article or revising it critically for important intellectual content. Bixia Liu and Lei Chen were responsible for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Gu Zhang was responsible for immunohistochemical detection. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.