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浆液性卵巢腺癌患者某些生物体液的代谢组学特征

The metabolomic profile features of some bio logical fluids in serous ovarian adenocarcinoma patients.

作者信息

Kutilin D S, Filippov F E, Guskova O N, Alliluev I A, Enin Y S, Maksimov A Y

出版信息

Klin Onkol. 2025;38(1):38-44. doi: 10.48095/ccko202538.

Abstract

BACKGROUND

The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient's biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS.

MATERIAL AND METHODS

To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library.

RESULTS

Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P < 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P < 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P < 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease.

CONCLUSION

The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.

摘要

背景

寻找有效的卵巢癌(OC)早期诊断生物标志物是现代肿瘤妇科的一项紧迫任务。通过超高效液相色谱和质谱联用(UHPLC-MS)进行代谢谱分析,可提供患者生物体液样本中所有低分子量代谢物的总体信息,反映体内发生的过程。本研究的目的是通过UHPLC-MS研究浆液性卵巢腺癌患者的血浆和尿液代谢组学特征。

材料与方法

为进行代谢组学分析,采集了60例被诊断为浆液性卵巢癌患者的血浆样本和60例尿液样本,以及20例明显健康志愿者的样本。在Vanquish Flex UHPLC系统色谱仪(德国赛默飞世尔科技公司)上进行色谱分离。在配备电喷雾电离源的Orbitrap Exploris 480(德国赛默飞世尔科技公司)上进行质谱分析。使用Compound Discoverer软件(美国赛默飞世尔科技公司)进行生物信息学分析,使用Python编程语言中的SciPy库进行统计数据分析。

结果

使用UHPLC-MS在血浆中鉴定出1049种不同类别的代谢物。与健康对照者相比,OC患者中有8种代谢物浓度显著降低(P<0.01),而19种化合物的含量则相反,有所增加(P<0.01)。在尿液样本的代谢组学分析中,鉴定出417种代谢物:与明显健康个体相比,12种化合物浓度显著降低,14种化合物含量增加(P<0.01)。在卵巢浆液性腺癌患者中,发现血浆和尿液代谢组有显著变化,表现为脂质及其衍生物、脂肪酸及其衍生物、酰基肉碱、磷脂、氨基酸及其衍生物、含氮碱基衍生物和类固醇的浓度异常。同时,犬尿氨酸、肉豆蔻酸、溶血磷脂酰胆碱和L-辛酰肉碱是该疾病最有前景的标志物。

结论

所揭示的代谢组变化可为改进浆液性卵巢腺癌的诊断方法提供依据。

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