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, C(16:1), C(18:3), C(18:2), C(18:1), C(20:4), and C(22:6)) 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, C(17:1) as IS of C(16:1), C(18:3), C(18:2), and C(18:1) and C(21:0 )as IS of C(20:4) and C(22:6)) 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 C(16:1), C(18:1), C(18:3), C(18:2), C(20:4), and C(22:6) 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 (C(16:1 )and C(18:1)) 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 C(16:1), C(18:1), C(18:3), C(18:2), C(20:4), and C(22:6) may be a powerful biomarker panel for the early detection of NSCLC and a combination of C(16:1 )and C(18:1)for disease progression monitoring of NSCLC.