Probing gender-specific lipid metabolites and diagnostic biomarkers for lung cancer using Fourier transform ion cyclotron resonance mass spectrometry

• Published in: Clinica chimica acta Vol. 414; pp. 135 - 141
• Main Authors: Guo, Yumei, Wang, Xianmin, Qiu, Ling, Qin, Xuzhen, Liu, Hui, Wang, Yanying, Li, Fang, Wang, Xiaodong, Chen, Guoqiang, Song, Gaoguang, Li, Fenjie, Guo, Shuai, Li, Zhili
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 24.12.2012
• Subjects: Biomarkers, Tumor - blood; Cyclotrons; Direct-infusion ESI-FTICR MS; Discriminant Analysis; Female; Fourier Analysis; Humans; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Lysophosphatidylcholines - metabolism; Male; Mass Spectrometry; Middle Aged; PLS-DA; Serum metabolites; Sex; Sphingomyelins - metabolism; Staging; Serum metabolites; Staging; MS; Lung cancer; ROC; Sex; PLS-DA; LOOCV; PRESS; DI‐ESI‐FTICR MS; PC; LC; SM; TN; TP; VIP; LPC; Direct-infusion ESI-FTICR MS
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2012.08.010

There are no effective clinical biomarkers for early and specific detection of lung cancer (LC). The changes in the levels of some serum metabolites of LC patients are associated with patient gender and LC stages. Serum metabolites of the LC patients (n=58) and healthy controls (n=495) were performed using direct-infusion positive ion electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry in combination with univariate and partial least squares discriminant analyses (PLS-DA). Univariate analysis indicated that 141 of the 212 serum metabolites were significantly changed in the LC patients compared with healthy controls. PLS-DA model, based on the 141 metabolites, demonstrated the differential metabolite distribution in single-sex LC patients compared with the corresponding healthy controls, and also in LC females compared with LC males. Several lipids comprising fatty acid derivations, sphingomyelin (SM) and lysophosphatidylcholine (LPC) were associated with the LC progression. Classification using oleamide, long chain acyl carnitines, LPC(18:1), LPC(20:4), LPC(20:3), LPC(22:6), and SM(16:0/1) as a biomarker panel resulted in remarkable separation between the LC patients and healthy controls with sensitivity and specificity of 100% and 91%, respectively. The serum metabolites found in this study may play essential roles in gender-specific LC detection and early diagnosis of cancer. ► Direct-infusion ESI-FTICR MS was used for lung cancer metabolite profiling. ► LC females and males have different metabolic behaviors. ► Changes in the levels of metabolites were associated with the LC progression. ► Identified metabolites could differentiate early-stage patients from healthy controls and LC patients from healthy controls. ► Biomarker panel had excellent diagnostic ability with sensitivity of 100% and specificity of more than 91%.