Serum Unsaturated Free Fatty Acids: Potential Biomarkers for Early Detection and Disease Progression Monitoring of Non-Small Cell Lung Cancer

BACKGROUND Lung cancer (LC) is the deadliest cancer, with earlier stage patients having a better opportunity of long-term survival. The goal of this study is to screen less-invasive and efficient biomarkers for early detection of non-small cell LC (NSCLC). MATERIAL AND METHODS We performed the simultaneous quantitative detection of six serum unsaturated free fatty acids (FFAs, C16:1, C18:3, C18:2, C18:1, C20:4, and C22:6) from 317 healthy controls, 78 patients with benign lung diseases (BLD), and 202 patients with NSCLC using chip-based direct-infusion nanoelectrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (CBDInanoESI-FTICR MS) in the negative ion mode. Multiple point internal standard calibration curves between the concentration ratios of individual fatty acids to internal standards (ISs, C17:1 as IS of C16:1, C18:3, C18:2, and C18:1 and C21:0 as IS of C20:4 and C22:6) and their corresponding intensity ratios were constructed, with correlation coefficient of > 0.99. Mann-Whitney U test was employed to compare the differences in the levels of the FFAs between the patients and healthy controls. RESULTS Significantly decreased levels of the FFAs in NSCLC patients were observed compared with healthy controls and BLD patients. Receiver operating characteristic curve analysis indicated that a combination of C16:1, C18:1, C18:3, C18:2, C20:4, and C22:6 could excellently differentiate patients with early-stage NSCLC from healthy controls plus BLD patients, with an AUC value of 0.933, a sensitivity of 84.2%, and a specificity of 89.1%. In addition, a biomarker panel (C16:1 and C18:1) was also confirmed preliminarily to monitor disease progression in NSCLC patients treated with icotinib, with a lead time between 8 and 48 weeks relative to clinical medical imaging. CONCLUSION A combination of C16:1, C18:1, C18:3, C18:2, C20:4, and C22:6 may be a powerful biomarker panel for the early detection of NSCLC and a combination of C16:1 and C18:1for disease progression monitoring of NSCLC.