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Published on: July 21, 2018
Expression and clinical significance of mTOR in surgically resected non-small cell lung cancer tissues: a case
Zhe Liu1, Liang Wang, Li-Na Zhang
1Department of Oncology, Beijing Chest Hospital, Capital Medical University of China, Beijing, China. liuzhe1968@yahoo.com.cn
Aims:
Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and 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 of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed.
Results:
The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent.
Conclusions:
Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.
Insights
Mammalian target of rapamycin (mTOR) signaling is dysregulated in non-small cell lung cancers (NSCLCs). Targeting mTOR in combination with IGF-1R and PTEN may offer new NSCLC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The mammalian target of rapamycin (mTOR) pathway is crucial in regulating cell growth and is implicated in non-small cell lung cancers (NSCLCs).
- Understanding the expression patterns of mTOR and its associated molecules like PTEN, IGF-1R, and 4EBP1 is vital for NSCLC pathogenesis.
Purpose of the Study:
- To characterize the mRNA and protein expression levels of mTOR and its regulators (PTEN, IGF-1R, 4EBP1) in NSCLC tissues.
- To investigate the associations between the expression of these molecules and clinical characteristics in NSCLC patients.
Main Methods:
- RT-PCR was used to quantify mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1.
- Immunohistochemistry (IHC) assessed protein expression of mTOR, PTEN, and IGF-1R.
- Statistical analyses explored correlations between molecular expression and clinical features.
Main Results:
- NSCLC tissues showed increased mTOR mRNA expression, while PTEN, 4EBP1, and IGF-1R mRNA levels decreased.
- High IGF-1R expression correlated with advanced clinical stage (Stage III); PTEN expression was inversely associated with tumor size.
- mTOR protein was detected in 51.8% of cases, IGF-1R in 83.3%, and PTEN loss in 46.3%.
Conclusions:
- Aberrant mTOR signaling, elevated IGF-1R, and reduced PTEN expression are prevalent in resected NSCLC.
- The limited concordance between mTOR and its regulators suggests combination therapies targeting mTOR inhibitors with other agents hold promise for NSCLC treatment.
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