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  3. Profiling the metabolome of uterine fluid for early detection of ovarian cancer

Profiling the metabolome of uterine fluid for early detection of ovarian cancer

  • Cell Rep Med. 2023 May 24;101061. doi: 10.1016/j.xcrm.2023.101061.
Pan Wang 1,  Jihong Ma 1,  Wenjing Li 1,  Qilong Wang 2,  Yinan Xiao 1,  Yuening Jiang 1,  Xiaoyang Gu 1,  Yu Wu 1,  Suwei Dong 3,  Hongyan Guo 4,  Mo Li 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing 100191, China.
  • 2 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 4 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing 100191, China. Electronic address: [email protected].
  • 5 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing 100191, China. Electronic address: [email protected].
PMID: 37267943 DOI: 10.1016/j.xcrm.2023.101061
Abstract

Ovarian Cancer (OC) causes high mortality in women because of ineffective biomarkers for early diagnosis. Here, we perform metabolomics analysis on an initial training set of uterine fluid from 96 gynecological patients. A seven-metabolite-marker panel consisting of vanillylmandelic acid, norepinephrine, phenylalanine, beta-alanine, tyrosine, 12-S-hydroxy-5,8,10-heptadecatrienoic acid, and crithmumdiol is established for detecting early-stage OC. The panel is further validated in an independent sample set from 123 patients, discriminating early OC from controls with an area under the curve (AUC) of 0.957 (95% confidence interval [CI], 0.894-1). Interestingly, we find elevated norepinephrine and decreased vanillylmandelic acid in most OC cells, resulting from excess 4-hydroxyestradiol that antagonizes the catabolism of norepinephrine by catechol-O-methyltransferase. Moreover, exposure to 4-hydroxyestradiol induces cellular DNA damage and genomic instability that could lead to tumorigenesis. Thus, this study not only reveals metabolic features in uterine fluid of gynecological patients but also establishes a noninvasive approach for the early diagnosis of OC.

Keywords

DNA damage; early diagnosis; metabolome; ovarian cancer; uterine fluid.

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