Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry.
BACKGROUND
Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC).


METHODS
Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay.


RESULTS
Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control.


CONCLUSIONS
The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers.


CONCLUSIONS
There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; BioNano Integration Research Group, Biotechnology Research Centre, Tripoli, Libya.
Abduladim
A
Hmmier
Department of Respiratory Medicine, Beaumont Hospital, Dublin 9, Ireland.
Michael Emmet
ME
O'Brien
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Vincent
V
Lynch
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Martin
M
Clynes
Department of Respiratory Medicine, Beaumont Hospital, Dublin 9, Ireland.
Ross
R
Morgan
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
Paul
P
Dowling
BALF; Biomarkers; ELISA; Mass spectrometry; Plasma; Proteomics