Identification of a Lung Cancer Biomarker Using a Cancer Cell Line and Screening of Olfactory Receptors for Biomarker Detection

Abstract

Several studies investigated the development of a non-invasive and early diagnostic method for cancer. Recently, the volatile organic compounds (VOCs) exhaled from cancer patients have been shown to act as a potential biomarker for cancer. However, the gas profile of breath is highly variable and not conducive to identification of biomarkers accurately. Accordingly, we identified a cancer-specific VOC as a biomarker using an in vitro cancer system in order to exclude the variables from patient condition. VOCs were collected from the headspace gas of lung cancer cell line (SK-MES) and normal lung cell line (MRC-5), followed by analysis using solid-phase microextraction (SPME)-GC/MS. As a result, 2-ethyl-1-hexanol was detected from headspace gas of SK-MES and decided as a potential biomarker for lung cancer. By screening human olfactory receptor libraries to detect a lung cancer biomarker, human olfactory receptor 4D11P (hOR4D11P) was identified as a receptor specific for 2-ethyl-1-hexanol and expressed heterologously in HEK293 cells. Additionally, we generated nanovesicles containing hOR4D11P from HEK293 cells and confirmed the expression and functionality of hOR4D11P in nanovesicles.