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利用超高效液相色谱/四极杆飞行时间质谱法鉴定卵巢癌患者血清中的潜在生物标志物并进行代谢谱分析

Identification of Potential Biomarkers and Metabolic Profiling of Serum in Ovarian Cancer Patients Using UPLC/Q-TOF MS.

作者信息

Yang Wanchao, Mu Tian, Jiang Jing, Sun Qintong, Hou Xuejia, Sun Yu, Zhong Lei, Wang Cheng, Sun Changhao

机构信息

Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, China.

出版信息

Cell Physiol Biochem. 2018;51(3):1134-1148. doi: 10.1159/000495492. Epub 2018 Nov 26.

Abstract

BACKGROUND/AIMS: Ovarian cancer (OC) is a malignant neoplasm of the female reproductive system with a high mortality rate. Identifying useful biomarkers and clarifying the molecular pathogenesis of OC are critical for early diagnosis and treatment. The aim of the study was to identify candidate biomarkers and explore metabolic changes of OC.

METHODS

A two-stage design was used in our study, with a discovery cohort of OC cases (n = 30) and controls (n = 30) and an independent cohort of cases (n = 17) and controls (n = 18) for validation. The serum metabolic profiling was investigated by ultra-performance liquid chromatography and quadrupole time-of-fight mass spectrometry with positive electrospray ionization.

RESULTS

A total of 18 metabolites closely related to OC were identified in the discovery stage, of which 12 were confirmed in the validation cohort. Metabolic pathways in OC related to these biomarkers included fatty acid β-oxidation, phospholipid metabolism, and bile acid metabolism, which are closely related to the proliferation, invasion, and metastasis of cancer cells. Multiple logistic regression analysis of these metabolites showed that 2-piperidinone and 1-heptadecanoylglycerophosphoethanolamine were potential biomarkers of OC, with high sensitivity (96.7%), specificity (66.7%), and area under the receiver operating characteristic curve value (0.894).

CONCLUSION

These findings provide insight into the pathogenesis pathogenesis of OC and may be useful for clinical diagnosis and treatment.

摘要

背景/目的:卵巢癌(OC)是女性生殖系统的一种恶性肿瘤,死亡率很高。识别有用的生物标志物并阐明OC的分子发病机制对于早期诊断和治疗至关重要。本研究的目的是识别候选生物标志物并探索OC的代谢变化。

方法

我们的研究采用两阶段设计,有一个由OC病例(n = 30)和对照(n = 30)组成的发现队列,以及一个由病例(n = 17)和对照(n = 18)组成的独立队列用于验证。通过超高效液相色谱和带正电喷雾电离的四极杆飞行时间质谱对血清代谢谱进行研究。

结果

在发现阶段共鉴定出18种与OC密切相关的代谢物,其中12种在验证队列中得到证实。与这些生物标志物相关的OC代谢途径包括脂肪酸β-氧化、磷脂代谢和胆汁酸代谢,这些都与癌细胞的增殖、侵袭和转移密切相关。对这些代谢物进行多元逻辑回归分析表明,2-哌啶酮和1-十七烷酰甘油磷酸乙醇胺是OC的潜在生物标志物,具有高灵敏度(96.7%)、特异性(66.7%)和受试者工作特征曲线下面积值(0.894)。

结论

这些发现为OC的发病机制提供了见解,可能对临床诊断和治疗有用。

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