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Serum lipidomic profiling by UHPLC-MS/MS may be able to detect early-stage endometrial cancer

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Abstract

Nowadays, screening for endometrial cancer (EC) primarily relies on clinical symptoms and imaging, which makes it difficult to detect early-stage disease. Here, we conducted a widely targeted lipidomic analysis of 38 human serum samples in a discovery set and 40 human serum samples in a validation set to profile the dysregulated lipid species and establish lipid biomarkers for early-stage EC. This comprehensive lipidomic determination of 616 serum lipids indicated significant differences between early-stage EC patients and healthy controls. Three phases of lipid biomarker investigation (discovery, validation, and determination of the lipid biomarker panel) were performed, which revealed the upregulation of some sphingolipid, glycerophospholipid, and glycerolipids and downregulation of some carnitine. Consistently, the perturbation of sphingolipid and glycerophospholipid metabolism was also observed from pathway enrichment analysis. Moreover, a lipid biomarker panel, including ursodeoxycholic acid, PC(O-14:0_20:4), and Cer(d18:1/18:0), was established. This panel was assessed as an effective diagnostic model to distinguish early-stage EC patients from healthy controls and atypical endometrial hyperplasia patients within the area under the receiver operating characteristic curve (AUC) reaching 0.903 and 0.928, respectively. In particular, the comparison results of the diagnostic efficacy indicated that the lipid biomarker panel was superior to clinically established indicators for EC diagnosis, including HE4, CA125, CA153, and CA199, suggesting that it could be used as an excellent supplementary method for the diagnosis of early-stage EC. In conclusion, we established a novel and non-invasive lipid biomarker for early-stage EC detection and these findings may provide new insight into the pathological mechanisms of EC.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors gratefully acknowledge all the participants who are recruited in this study. We would like to thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This work was supported by the Special Funds for Health Science and Technology Development of Nanjing City (Grant Numbers: YKK21161, YKK20137).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No 123, Tianfei Lane, Mochou Road, Qinhuai District, Nanjing, 210000, Jiangsu, China

    Feng Cheng, Weimin Fan, Ling Gui, Yixian Liu, Yu Ling, Rong Huang, Zhifa Wen & Yajun Chen

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  1. Feng Cheng
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Contributions

YJ-C: contributed to experimental design, supervision, and original draft preparation. FC and ZF-W: contributed to original draft preparation, revision of the manuscript, and funding acquisition. WM-F, LG, and YX-L: contributed to the revision of the manuscript, and data collection and analysis. RH and YL: contributed to sample collection and data validation. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Feng Cheng, Zhifa Wen or Yajun Chen.

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This study was authorized by the ethics committee of the Women’s Hospital of Nanjing Medical University (2021KY-036) and executed strictly following the Declaration of Helsinki. Written formal consents were acquired from all of the participants.

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The authors declare no competing interests.

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Cheng, F., Fan, W., Gui, L. et al. Serum lipidomic profiling by UHPLC-MS/MS may be able to detect early-stage endometrial cancer. Anal Bioanal Chem 415, 1841–1854 (2023). https://doi.org/10.1007/s00216-023-04586-x

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