Abstract

Protein Profiling of Tumour-derived Exosomes for Plasma Biomarker Discovery in Non-Small Cell Lung Cancer

Lingzhi Wang, Senior Research Scientist, Ctr. for Translational Medicine, Adjunct Professor, National University of Singapore

Lung cancers are often diagnosed at advanced stages with concomitant poor prognosis, making it the leading cause of cancer mortality worldwide. Although low-dose CT have shown to be useful in detecting small abnormalities in the lung and associated with a 20% reduction in lung cancer-specific mortality, they have also been found to have high false positive rate of detection (96.4%) in a recent U.S.A. National screening trial. It is thus important to identify novel minimally-invasive lung cancer biomarkers. Circulating exosomes are important resources for cancer biomarker discovery because exosomes can reflect the cell’s RNA and protein contents from which they are secreted. In our study, Linear Trap Quadrupole Fourier Transform (LTQ-FT) mass spectrometry was adopted for protein profiling of the exosomes isolated from a normal lung fibroblast and three lung cancer cell lines. A total of 2983 proteins were identified from all the four cell lines-derived exosomes. Importantly, current lung cancer protein biomarkers such as CEA, CYFRA 21-1, CA-125 and NSE were also detected in our identifications. A panel of exosomal proteins have been identified as biomarker candidates based on bioinformatics analysis. In particular, FAM3C was found to be expressed differentially between NSCLC patients and healthy volunteers’ plasma samples, suggesting that it may have the potential to become diagnostic biomarker for lung cancer. In addition, IHC staining of NSCLC tissue array revealed granular FAM3C localization was significantly associated with improved lung cancer specific survival in squamous cell lung carcinoma patients, suggesting that FAM3C could be a potential prognostic biomarker. In vitro functional study demonstrated that FAM3C was correlated with cell proliferation and metastasis of lung cancer cells. A large-scale clinical study is now ongoing to validate the utility of FAM3C as a plasma biomarker for NSCLC.