Zhang Yaping, He Chengyan, Qiu Ling, Wang Yanmin, Zhang Li, Qin Xuzhen, Liu Yujie, Zhang Dan, Li Zhili
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;
J Cancer. 2014 Sep 19;5(8):706-14. doi: 10.7150/jca.9787. eCollection 2014.
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).
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.
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.
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.
肺癌是最致命的癌症，早期患者有更好的长期生存机会。本研究的目的是筛选用于早期检测非小细胞肺癌（NSCLC）的侵入性较小且有效的生物标志物。
我们使用基于芯片的直接进样纳米电喷雾电离 - 傅里叶变换离子回旋共振质谱（CBDInanoESI - FTICR MS）负离子模式，对317名健康对照者、78名良性肺病（BLD）患者和202名NSCLC患者的六种血清不饱和游离脂肪酸（FFAs，C16:1、C18:3、C18:2、C18:1、C20:4和C22:6）进行了同步定量检测。构建了各个脂肪酸与内标（ISs，C17:1作为C16:1、C18:3、C18:2和C18:1的内标，C21:0作为C20:4和C22:6的内标）浓度比与其相应强度比之间的多点内标校准曲线，相关系数>0.99。采用曼 - 惠特尼U检验比较患者与健康对照者之间FFAs水平的差异。
与健康对照者和BLD患者相比，NSCLC患者的FFAs水平显著降低。受试者工作特征曲线分析表明，C16:1、C18:1、C18:3、C18:2、C20:4和C22:6的组合能够很好地区分早期NSCLC患者与健康对照者加BLD患者，曲线下面积（AUC）值为0.933，灵敏度为84.2%，特异性为89.1%。此外还初步证实了一个生物标志物组合（C16:1和C18:1）可用于监测接受埃克替尼治疗的NSCLC患者的疾病进展，相对于临床医学影像，其提前期为8至48周。
C16:1、C18:1、C18:3、C18:2、C20:4和C22:6的组合可能是用于早期检测NSCLC的强大生物标志物组合，而C16:1和C18:1的组合可用于监测NSCLC的疾病进展。
