J Cancer 2014; 5(8):706-714. doi:10.7150/jca.9787

Research Paper

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

Yaping Zhang1, Chengyan He2, Ling Qiu3, Yanmin Wang4, Li Zhang5, Xuzhen Qin3, Yujie Liu1, Dan Zhang1, Zhili Li1✉

1. Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China;
2. Laboratory Medicine Center, China-Japan Union Hospital of Jilin University, Changchun, China;
3. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;
4. Department of Clinical Laboratory, Heze Municipal Hospital, Heze, China;
5. Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Abstract

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.

Keywords: non-small cell lung cancer, biomarker panel, early detection, unsaturated free fatty acids, serum.

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How to cite this article:
Zhang Y, He C, Qiu L, Wang Y, Zhang L, Qin X, Liu Y, Zhang D, Li Z. Serum Unsaturated Free Fatty Acids: Potential Biomarkers for Early Detection and Disease Progression Monitoring of Non-Small Cell Lung Cancer. J Cancer 2014; 5(8):706-714. doi:10.7150/jca.9787. Available from http://www.jcancer.org/v05p0706.htm