Identification of predictive biomarkers for diagnosis and radiation sensitivity of uterine cervical cancer using wide‐targeted metabolomics

Author:

Hishinuma Eiji12,Shimada Muneaki13ORCID,Matsukawa Naomi2,Li Bin12,Motoike Ikuko N.24,Hagihara Tatsuya3,Shigeta Shogo3ORCID,Tokunaga Hideki3ORCID,Saigusa Daisuke25,Kinoshita Kengo124,Koshiba Seizo12,Yaegashi Nobuo123

Affiliation:

1. Advanced Research Center for Innovations in Next‐Generation Medicine Tohoku University Sendai Japan

2. Tohoku Medical Megabank Organization Tohoku University Sendai Japan

3. Department of Gynecology and Obstetrics, Graduate School of Medicine Tohoku University Sendai Japan

4. Systems Bioinformatics, Graduate School of Information Sciences Tohoku University Sendai Japan

5. Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma‐Science Teikyo University Tokyo Japan

Abstract

AbstractAimUterine cervical cancer (UCC) is the fourth most common cancer in women, responsible for more than 300 000 deaths worldwide. Its early detection, by cervical cytology, and prevention, by vaccinating against human papilloma virus, greatly contribute to reducing cervical cancer mortality in women. However, penetration of the effective prevention of UCC in Japan remains low. Plasma metabolome analysis is widely used for biomarker discovery and the identification of cancer‐specific metabolic pathways. Here, we aimed to identify predictive biomarkers for the diagnosis and radiation sensitivity of UCC using wide‐targeted plasma metabolomics.MethodsWe analyzed 628 metabolites in plasma samples obtained from 45 patients with UCC using ultra‐high‐performance liquid chromatography with tandem mass spectrometry.ResultsThe levels of 47 metabolites were significantly increased and those of 75 metabolites were significantly decreased in patients with UCC relative to healthy controls. Increased levels of arginine and ceramides, and decreased levels of tryptophan, ornithine, glycosylceramides, lysophosphatidylcholine, and phosphatidylcholine were characteristic of patients with UCC. Comparison of metabolite profiles in groups susceptible and non‐susceptible to radiation therapy, a treatment for UCC, revealed marked variations in polyunsaturated fatty acid, nucleic acid, and arginine metabolism in the group not susceptible to treatment.ConclusionsOur findings suggest that the metabolite profile of patients with UCC may be an important indicator for distinguishing these patients from healthy cohorts, and may also be useful for predicting sensitivity to radiotherapy.

Funder

Japan Agency for Medical Research and Development

Publisher

Wiley

Subject

Obstetrics and Gynecology

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