Lung cancer (Lca) is one of the malignant tumors with the fastest morbidity and mortality increase and the greatest threat to human health and life. The incidence of non-small cell lung cancer (NSCLC) in the nonsmoking female has increased recently. However, its pathogenesis is still unclear, and there is an urgent need for clinical diagnostic biomarkers, especially for early diagnosis. A nontargeted lipidomic approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), as well as two machine learning approaches (genetic algorithm and binary logistic regression) was used to screen candidate discriminating lipids and define a combinational lipid biomarker in serum samples to distinguish female patients with NSCLC from healthy controls. Moreover, the candidate biomarkers were verified by using an external validation sample set. Our result revealed that fatty acid (FA) (20:4), FA (22:0) and LPE (20:4) can serve as a combinational biomarker for distinguishing female patients with NSCLC from healthy control with good sensitivity and specificity. Furthermore, this combinational biomarker also showed good performance in distinguishing early-stage NSCLC female patients from a healthy control. We observed that levels of unsaturated fatty acids clearly decreased, while saturated fatty acids and lysophosphatidylethanolamines pronouncedly increased in Lca patients, compared with the healthy controls, which revealed significant disturbance of lipid metabolism in NSCLC females. Our results not only provide hints to the pathological mechanism of NSCLC in nonsmoking female but also supply a combinational lipid biomarker to aid the diagnosis of NSCLC at early-stage.

中文翻译：

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非吸烟女性患者的非小细胞肺癌血清脂质组学标志物。

肺癌（Lca）是发病率和死亡率增加最快，对人类健康和生命构成最大威胁的恶性肿瘤之一。非吸烟女性中非小细胞肺癌（NSCLC）的发病率最近有所增加。然而，其发病机理仍不清楚，并且迫切需要临床诊断生物标志物，尤其是早期诊断。使用了基于超高效液相色谱和四极杆飞行时间质谱（UHPLC-Q-TOF / MS）的非靶向脂质组学方法，以及两种机器学习方法（遗传算法和二进制逻辑回归）筛选候选鉴别性脂质并在血清样品中定义组合脂质生物标志物，以将女性NSCLC患者与健康对照区分开。此外，通过使用外部验证样本集来验证候选生物标记。我们的结果表明，脂肪酸（FA）（20：4），FA（22：0）和LPE（20：4）可以作为组合生物标志物，以良好的敏感性和特异性将女性NSCLC患者与健康对照区分开。此外，这种组合生物标志物在区分早期NSCLC女性患者和健康对照方面也显示出良好的性能。我们观察到，与健康对照组相比，Lca患者的不饱和脂肪酸水平明显降低，而饱和脂肪酸和溶血磷脂酰乙醇胺明显升高，这表明NSCLC女性的脂质代谢受到严重干扰。