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Q Exactive 液相色谱/串联质谱筛选鉴定出胆碱、25-羟基维生素 D2 和 SM(d18:0/16:1(9Z) (OH)) 可作为高级别浆液性卵巢癌的生物标志物。

Screening by Q Exactive liquid chromatography/tandem mass spectrometry identified Choline, 25-hydroxyvitamin D2, and SM(d18:0/16:1(9Z) (OH)) as biomarkers for high-grade serous ovarian cancer.

机构信息

Department of Gynecologic Oncology, Gynecologic and Obstetrics Centre, the First Hospital of Jilin University, Changchun, Jilin 130012, China.

First Department of General Gynecology, Gynecologic and Obstetrics Centre, The First Hospital of Jilin University, Changchun 130021, Jilin, China.

出版信息

J Proteomics. 2024 May 15;299:105154. doi: 10.1016/j.jprot.2024.105154. Epub 2024 Mar 11.

Abstract

High-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (22 HGSOC samples and 22 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC)  ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery SIGNIFICANCE: High-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (20 HGSOC samples and 20 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery.

摘要

高级别浆液性卵巢癌 (HGSOC) 死亡率高,预后差。预后不良的主要原因是疾病早期无症状、目前尚无有效的筛查方法,以及疾病晚期。细胞代谢的变化是癌症的特征,而血浆代谢组学分析可用于鉴定生物标志物。在这项研究中,我们使用 Q Exactive 液相色谱串联质谱法 (LC-MS/MS,QE) 比较了血浆样本(22 例 HGSOC 样本和 22 例正常样本)之间的差异。总共检测到 124 种代谢物,正交偏最小二乘判别分析 (OPLS-DA) 模型可有效区分 HGSOC 患者与健康对照者。在基于 Q Exactive LC/MS/MS 方法验证的血浆代谢组学方法中,使用学生 t 检验,当投影变量重要性 (VIP) > 1、p < 0.05 时,胆碱、25-羟基维生素 D2 和鞘磷脂 (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) 在 HGSOC 患者的血浆中显示出明显差异水平,且倍数变化 (FC)≥1.5 或≤0.667。代谢途径分析可以提供有价值的信息,增强对 HGSOC 潜在病理生理学的理解。总之,基于 Q Exactive LC/MS/MS 方法验证的血浆代谢组学方法可能具有作为 HGSOC 便捷筛查方法的潜力,也可能是监测 HGSOC 术后患者肿瘤复发的一种方法。

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