Identification of Novel Serum Metabolic Biomarkers as Indicators in the Progression of Intravenous Leiomyomatosis: A High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Study.

HPLC-MS/MS biomarkers intravenous leiomyomatosis metabolomics progression

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2021
Historique:
received: 15 04 2021
accepted: 18 06 2021
entrez: 26 7 2021
pubmed: 27 7 2021
medline: 27 7 2021
Statut: epublish

Résumé

Intravenous leiomyomatosis (IVL) is a rare estrogen-dependent neoplasm. However, identifiable and reliable biomarkers are still not available for clinical application, especially for the diagnosis and prognosis of the disease. In the present study, 30 patients with IVL and 30 healthy controls were recruited. Serum samples were isolated from these participants for further high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis to study metabolomics alterations and identify differentially expressed metabolites based on orthogonal partial least-squares discriminant analysis (OPLS-DA). Subsequently, lasso regression analysis and a generalized linear regression model were applied to screen out hub metabolites associated with the progression of IVL. First, 16 metabolites in the positive ion mode were determined from the 240 identifiable metabolites at the superclass level, with ten metabolites upregulated in the IVL group and the remaining six metabolites downregulated. Our data further proved that four metabolites [hypoxanthine, acetylcarnitine, glycerophosphocholine, and hydrocortisone (cortisol)] were closely related to the oncogenesis of IVL. Hypoxanthine and glycerophosphocholine might function as protective factors in the development of IVL (OR = 0.19 or 0.02, respectively). Nevertheless, acetylcarnitine and hydrocortisone (cortisol), especially the former, might serve as risk indicators for the disease to promote the development or recurrence of IVL (OR = 18.16 or 2.10, respectively). The predictive accuracy of these hub metabolites was further validated by the multi-class receiver operator characteristic curve analysis (ROC) with the Scikit-learn algorithms. Four hub metabolites were finally determined via comprehensive bioinformatics analysis, and these substances could potentially serve as novel biomarkers in predicting the prognosis or progression of IVL.

Sections du résumé

BACKGROUND BACKGROUND
Intravenous leiomyomatosis (IVL) is a rare estrogen-dependent neoplasm. However, identifiable and reliable biomarkers are still not available for clinical application, especially for the diagnosis and prognosis of the disease.
METHODS METHODS
In the present study, 30 patients with IVL and 30 healthy controls were recruited. Serum samples were isolated from these participants for further high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis to study metabolomics alterations and identify differentially expressed metabolites based on orthogonal partial least-squares discriminant analysis (OPLS-DA). Subsequently, lasso regression analysis and a generalized linear regression model were applied to screen out hub metabolites associated with the progression of IVL.
RESULTS RESULTS
First, 16 metabolites in the positive ion mode were determined from the 240 identifiable metabolites at the superclass level, with ten metabolites upregulated in the IVL group and the remaining six metabolites downregulated. Our data further proved that four metabolites [hypoxanthine, acetylcarnitine, glycerophosphocholine, and hydrocortisone (cortisol)] were closely related to the oncogenesis of IVL. Hypoxanthine and glycerophosphocholine might function as protective factors in the development of IVL (OR = 0.19 or 0.02, respectively). Nevertheless, acetylcarnitine and hydrocortisone (cortisol), especially the former, might serve as risk indicators for the disease to promote the development or recurrence of IVL (OR = 18.16 or 2.10, respectively). The predictive accuracy of these hub metabolites was further validated by the multi-class receiver operator characteristic curve analysis (ROC) with the Scikit-learn algorithms.
CONCLUSION CONCLUSIONS
Four hub metabolites were finally determined via comprehensive bioinformatics analysis, and these substances could potentially serve as novel biomarkers in predicting the prognosis or progression of IVL.

Identifiants

pubmed: 34307370
doi: 10.3389/fcell.2021.695540
pmc: PMC8297591
doi:

Types de publication

Journal Article

Langues

eng

Pagination

695540

Informations de copyright

Copyright © 2021 Ge, Feng, Zhang, Li and Yu.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Zhitong Ge (Z)

Department of Ultrasound, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Penghui Feng (P)

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Zijuan Zhang (Z)

Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Jianchu Li (J)

Department of Ultrasound, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Qi Yu (Q)

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Classifications MeSH