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采用超高效液相色谱-串联质谱法筛选和鉴定非小细胞肺癌潜在的新型脂质生物标志物。

Screening and identification of potential novel lipid biomarkers for non-small cell lung cancer using ultra-high performance liquid chromatography tandem mass spectrometry.

机构信息

Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China.

出版信息

Anat Rec (Hoboken). 2022 May;305(5):1087-1099. doi: 10.1002/ar.24725. Epub 2021 Aug 23.

Abstract

Lung cancer is characterized by a high incidence rate and low survival rate. It is important to achieve early diagnosis of the disease. We applied ultra-high performance liquid chromatography tandem mass spectrometry to screen plasma lipid spectrum in non-small cell lung cancer (NSCLC) patients, healthy controls (HC), and community-acquired pneumonia (CAP) patients. Modeling employing orthogonal partial least squares-discriminant analysis combined with t-test was used to screen the differential lipids. Logistic regression analysis was used to establish the diagnostic model, while the accuracy was verified by 10-fold cross-validation. The results showed that the abnormal metabolism of lipid in NSCLC mainly comprised fatty acid metabolism, phospholipid metabolism, and glyceride metabolism. Four potential biomarkers, including LPC (14:0/0:0), LPI (14:1/0:0), DG (14:0/18:2/0:0), and LPC (16:1/0:0), were fitted by the receiver operating characteristic curve model with the area under curve (AUC) value of 0.856, and the specificity and sensitivity were 87.0 and 78.0%, respectively. The results of cross validation showed that the AUC value of the model was 0.812, the sensitivity was 72.9%, and the specificity was 82.6%. The positive rate of four potential lipid biomarkers in this study (>60.0%) was higher than that of existing tumor biomarkers in the clinical application. We investigated the plasma lipid profile of NSCLC patients and identified lipid biomarkers with potential diagnostic values. From the lipidomics perspective, our study may lay a foundation for the biomarker-based early diagnosis of lung cancer.

摘要

肺癌的发病率和存活率均较高,实现早期诊断至关重要。我们应用超高效液相色谱-串联质谱技术对非小细胞肺癌(NSCLC)患者、健康对照(HC)和社区获得性肺炎(CAP)患者的血浆脂质谱进行了筛选。采用正交偏最小二乘判别分析与 t 检验相结合的建模方法筛选差异脂质。利用 logistic 回归分析建立诊断模型,并通过 10 折交叉验证验证准确性。结果表明,NSCLC 患者脂质代谢异常主要涉及脂肪酸代谢、磷脂代谢和甘油酯代谢。通过受试者工作特征曲线模型拟合得到 4 种潜在的生物标志物,包括 LPC(14:0/0:0)、LPI(14:1/0:0)、DG(14:0/18:2/0:0)和 LPC(16:1/0:0),曲线下面积(AUC)值为 0.856,特异性和灵敏度分别为 87.0%和 78.0%。交叉验证结果显示模型的 AUC 值为 0.812,灵敏度为 72.9%,特异性为 82.6%。本研究中 4 种潜在脂质生物标志物的阳性率(>60.0%)高于临床应用中现有肿瘤生物标志物。我们研究了 NSCLC 患者的血浆脂质谱,鉴定了具有潜在诊断价值的脂质生物标志物。从脂质组学角度看,本研究可能为基于生物标志物的肺癌早期诊断奠定基础。

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