Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTORi n carcinogenesis, its prognostic potential inlung cancer has not beeninvestigated.Here,we quantitatively assessedmTORprotein expression in two large data sets to investigate the impact ofmTORexpression on patient survival. Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assessmTORexpression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation. Results: Tumors expressed mTOR in the cytoplasmin 56% and 50% of the cases in training and validation cohorts, respectively; mTORe xpression was not associated with standard clinical or pathologic characteristics. Patients with high mTORe xpression had a longer median overall survival comparedwith the lowexpressers (52.7 versus 38.5months; log rank P = 0.06), whichwas more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively). Conclusions: mTORex pression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTORin to clinical decisions.
ASJC Scopus subject areas
- Cancer Research