Screening and verifying endometrial carcinoma diagnostic biomarkers based on a urine metabolomic profiling study using UPLC-Q-TOF/MS

Clin Chim Acta. 2016 Dec 1:463:200-206. doi: 10.1016/j.cca.2016.10.027. Epub 2016 Oct 23.

Abstract

Background: Endometrial carcinoma (EOC) is a gynecological disease with one of the highest worldwide incidences. Due to the lack of typical clinical symptoms and limited sensitive screening methods used to diagnose endometrial carcinoma, the disease is easily neglected before patients are aware of its presence. Therefore, EOC results in serious impacts on women's lives and health. We screened diagnostic biomarkers of EOC with a noninvasive method that compared healthy individuals and endometrial hyperplasia (EOH) patients.

Methods: The morning urine of 25 healthy individuals, 25 patients with EOC and 10 patients with EOH were analyzed using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) platform. Metabolomics data were used to screen the different metabolites according to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) analyses. Furthermore, the screened biomarkers of the newly diagnosed EOC and EOH candidates and healthy individuals were verified using the predictive model of the support vector machine (SVM) to obtain EOC diagnostic biomarkers.

Results: An EOC diagnostic biomarker group was found according to the metabolomics method. Five diagnostic biomarkers, including porphobilinogen, acetylcysteine, N-acetylserine, urocanic acid and isobutyrylglycine, were significantly changed in the EOC patients. Among them, porphobilinogen and acetylcysteine were significantly down-regulated, while N-acetylserine, urocanic acid and isobutyrylglycine were significantly up-regulated.

Conclusions: Disturbances in these biomarkers have negative impacts on the body's metabolic functioning. The EOC diagnostic biomarker group can provide a clinical reference for diagnosing EOC and insight into the diagnosis of other diseases in the clinic.

Keywords: Diagnostic biomarkers; Endometrial carcinoma; Metabolomics.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Biomarkers, Tumor / urine*
  • Chromatography, High Pressure Liquid
  • Discriminant Analysis
  • Endometrial Hyperplasia / diagnosis
  • Endometrial Hyperplasia / urine
  • Endometrial Neoplasms / diagnosis*
  • Endometrial Neoplasms / urine*
  • Female
  • Humans
  • Mass Spectrometry
  • Metabolomics*

Substances

  • Biomarkers, Tumor