Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions.
Date
2016-01-01Author
Puglisi, M
Stewart, A
Thavasu, P
Frow, M
Carreira, S
Minchom, A
Punwani, R
Bhosle, J
Popat, S
Ratoff, J
de Bono, J
Yap, TA
O''Brien, M
Banerji, U
Type
Journal Article
Metadata
Show full item recordAbstract
OBJECTIVES: We hypothesised that it was possible to quantify phosphorylation of important nodes in the phosphatidylinositol 3-kinase (PI3K) pathway in cancer cells isolated from pleural effusions of patients with non-small cell lung cancer (NSCLC) and study their correlation to somatic mutations and clinical outcomes. MATERIALS AND METHODS: Cells were immunomagnetically separated from samples of pleural effusion in patients with NSCLC. p-AKT, p-S6K and p-GSK3β levels were quantified by ELISA; targeted next-generation sequencing was used to characterise mutations in 26 genes. RESULTS: It was possible to quantify phosphoproteins in cells isolated from 38/43 pleural effusions. There was a significant correlation between p-AKT and p-S6K levels [r = 0.85 (95% confidence interval 0.73-0.92), p < 0.0001], but not p-AKT and p-GSK3β levels [r = 0.19 (95% confidence interval -0.16 to 0.5), p = 0.3]. A wide range of mutations was described and p-S6K was higher in samples that harboured at least one mutation compared to those that did not (p = 0.03). On multivariate analysis, p-S6K levels were significantly associated with poor survival (p < 0.01). CONCLUSION: Our study has shown a correlation between p-AKT levels and p-S6K, but not GSK3β, suggesting differences in regulation of the distal PI3K pathway by AKT. Higher p-S6K levels were associated with adverse survival, making it a critically important target in NSCLC.
Collections
Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Pleural Effusion, Malignant
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction
Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Neoplastic Cells, Circulating
Phosphatidylinositol 3-Kinase
Glycogen Synthase Kinase 3 beta
Research team
Cancer Biomarkers
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours
Language
eng
Date accepted
2016-02-23
License start date
2016-01
Citation
Oncology, 2016, 90 (5), pp. 280 - 288
Publisher
KARGER