Expression and Clinical Significance of mTOR in Surgically Resected Non-small Cell Lung Cancer Tissues: a Case Control Study

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway andplays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTORand its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs.
Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study.mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression ofmTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant moleculeswith clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were alsoassessed.
Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, whilePTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated withadvanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). Theresults of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN andIGF-1R, to some extent.
Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, andloss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with itsregulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets holdsignificant potential for NSCLC treatment.