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探索代谢组学生物标志物以评估宫颈癌同步放化疗的疗效。

Exploring metabolomics biomarkers for evaluating the effectiveness of concurrent radiochemotherapy for cervical cancers.

作者信息

Zhou Huihui, Li Qi, Wang Tong, Liang Hong, Wang Yanan, Duan Yani, Song Min, Wang Yaoxian, Jin Hong

机构信息

Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.

Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China.

出版信息

Transl Cancer Res. 2020 Apr;9(4):2734-2747. doi: 10.21037/tcr.2020.02.49.

DOI:10.21037/tcr.2020.02.49
PMID:35117632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8797309/
Abstract

BACKGROUND

Cervical cancer is the second most common female malignancy worldwide. The main method to evaluate the effect of concurrent chemoradiotherapy (CCRT) in the locally advanced stage is imaging which cannot meet the clinical needs. This study aimed to explore potential cervical cancer biomarkers via plasma metabolomics and evaluate the effectiveness of CCRT and disease progression.

METHODS

Twenty-four primary and thirty recurrent patients were enrolled between November 2016 and November 2017. Plasma samples were obtained by centrifugation of whole blood collected from enrolled patients at admission and from primary patients after CCRT. Plasma metabolic profiles were determined via ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Multivariate analyses and public databases were used to screen and identify differential metabolites. Pathway analysis was conducted using MetaboAnalyst.

RESULTS

Metabolic profiles obtained were significantly different among primary, post-CCRT-treated, and recurrent patients. Multivariate analyses showed that 37 metabolites differed significantly among the three groups, of which the levels of 22 metabolites changed significantly after CCRT and recovered or even exceeded the levels in primary patients when the tumor reappeared. These 22 metabolites were mainly lipids involved in sphingolipid and glycerophospholipid metabolism. Among them, 8 metabolites with area under curve values above 0.75 between each pair of groups exhibited great potential for evaluating CCRT effectiveness and disease progression.

CONCLUSIONS

Our results show significantly different plasma metabolic profiles among the three cervical cancer groups; 8 metabolites were identified as potential biomarkers to evaluate the effectiveness of CCRT and disease progression, which can help evaluate the prognosis and treatment of cervical cancer in a timely manner.

摘要

背景

宫颈癌是全球第二常见的女性恶性肿瘤。评估同步放化疗(CCRT)对局部晚期宫颈癌疗效的主要方法是影像学检查,但该方法无法满足临床需求。本研究旨在通过血浆代谢组学探索潜在的宫颈癌生物标志物,并评估CCRT的疗效及疾病进展情况。

方法

2016年11月至2017年11月期间纳入24例初治患者和30例复发患者。通过对入组患者入院时采集的全血以及初治患者CCRT后采集的全血进行离心获取血浆样本。采用超高效液相色谱-四极杆飞行时间质谱法测定血浆代谢谱。运用多变量分析和公共数据库筛选并鉴定差异代谢物。使用MetaboAnalyst进行通路分析。

结果

初治患者、CCRT治疗后患者和复发患者的代谢谱存在显著差异。多变量分析显示,三组间有37种代谢物存在显著差异,其中22种代谢物在CCRT后水平发生显著变化,肿瘤复发时恢复甚至超过初治患者水平。这22种代谢物主要是参与鞘脂和甘油磷脂代谢的脂质。其中,每组间曲线下面积值大于0.75的8种代谢物在评估CCRT疗效和疾病进展方面具有很大潜力。

结论

我们的结果显示,三组宫颈癌患者的血浆代谢谱存在显著差异;8种代谢物被鉴定为评估CCRT疗效和疾病进展的潜在生物标志物,有助于及时评估宫颈癌的预后和治疗情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/75754a1d61f5/tcr-09-04-2734-fS.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/2fe3a2534352/tcr-09-04-2734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/3c84deb71a0c/tcr-09-04-2734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/946ec85c429a/tcr-09-04-2734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/88fbff08b7f7/tcr-09-04-2734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/6f7ebfb18c74/tcr-09-04-2734-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/e9e869716643/tcr-09-04-2734-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/a569d17e8e71/tcr-09-04-2734-fS.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/4072c0d9e907/tcr-09-04-2734-fS.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/75754a1d61f5/tcr-09-04-2734-fS.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/2fe3a2534352/tcr-09-04-2734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/3c84deb71a0c/tcr-09-04-2734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/946ec85c429a/tcr-09-04-2734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/88fbff08b7f7/tcr-09-04-2734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/6f7ebfb18c74/tcr-09-04-2734-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/e9e869716643/tcr-09-04-2734-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/a569d17e8e71/tcr-09-04-2734-fS.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/4072c0d9e907/tcr-09-04-2734-fS.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/8797309/75754a1d61f5/tcr-09-04-2734-fS.3.jpg

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