Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry

Abstract

BackgroundLung 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).MethodsUsing 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.ResultsFour 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.ConclusionThe results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers.General significanceThere 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.

In‐Depth Proteomic Analysis of Human Bronchoalveolar Lavage Fluid toward the Biomarker Discovery for Lung Cancers

“…Thus, many plasma proteins were detected in BALF, indicating that BALF is a great source of biomarkers for lung cancer. Indeed, these findings are in line with that of other studies published elsewhere (e.g., ANXA2) …”

“…[7] Recent studies have demonstrated potential usefulness of cancerassociated proteins, nucleic acid, and extracellular vesicles in the BALF for early detection and molecular characterization of lung cancer. [8][9][10] Proteomics is an emerging technology to quickly survey altered cellular functions through a large-scale gene determination and, therefore has been employed in a variety of clinical studies. [11,12] However, potential biomarker proteins in body fluids are often present at low levels, requiring sensitive techniques.…”

“…Indeed, these findings are in line with that of other studies published elsewhere (e.g., ANXA2). [10,18] Since BALF were directly collected from the tumor environment than plasma, we expected that biomarkers for lung cancer may exist in higher concentration in BALF than in blood. A list of 64 potential lung cancer biomarkers reported by Zamay et al was used to investigate an estimated concentration of biomarkers in BALF and plasma.…”

“…BALF has its merit in that it can provide a variety of information including immunologic, inflammatory, and infectious processes that occur at the lung parenchyma . Recent studies have demonstrated potential usefulness of cancer‐associated proteins, nucleic acid, and extracellular vesicles in the BALF for early detection and molecular characterization of lung cancer …”

Dose Dependent Synergism from Combination of Platinum Drugs with Curcumin Sgainst Colorectal Cancer Cell Lines

“…However downregulation of the protein in cisplatin resistant esophageal cell line and lung cancer has also been reported (Lai, Chan et al 2016;Hmmier, O'Brien et al 2017). In the present study, the protein was upregulated following the treatments of Cur alone and synergistic combined treatment of Ox with using bolus administration but downregulated after the treatment of Ox alone.…”