Simultaneous Quantification of Serum Nonesterified and Esterified Fatty Acids as Potential Biomarkers to Differentiate Benign Lung Diseases from Lung Cancer

In this study, we have employed graphene oxide as a matrix to simultaneously and directly quantify serum nonesterified and esterified fatty acids (FAs) using matrix-assisted laser/desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). Twelve serum nonesterified FAs combined with their individual esterified FAs (i.e., C(16:0), C(16:1), C(18:0), C(18:1), C(18:2), C(18:3), C(20:2), C(20:3), C(20:4), C(20:5), C(22:5), and C(22:6)) were quantified based on their calibration curves with the correlation coefficients of >0.99, along with the analytical time of <1 min each sample. As a result, serum levels of twelve total FAs (TFAs) in 1440 serum samples from 487 healthy controls (HCs), 479 patients with benign lung diseases (BLDs) and 474 patients with lung cancer (LC) were determined. Statistical analysis indicated that significantly increased levels of C(16:0), C(16:1), C(18:0), C(18:1), C(18:3), C(20:3), and C(22:6) and decreased levels of C(20:5) were observed in LC patients compared with BLDs. Receiver operating characteristic (ROC) analysis revealed that panel a (C(18:2), C(20:3), C(20:4), C(20:5), C(22:5), and C(22:6)), panel b (C(18:0), C(20:4), C(20:5), and C(22:6)), and panel c (C(16:1), C(18:0), C(18:1), C(20:3), and C(22:6)) have exhibited good diagnostic ability to differentiate BLDs from LC relative to clinical uses of tumor markers (CEA and Cyfra 21-1).