Prognostic biomarkers of cervical squamous cell carcinoma identified via plasma metabolomics

Cervical cancer is the second most common female malignancy worldwide. The metabolic profile of plasma associated with the prognosis of cervical cancer remains poorly understood. In this cross-sectional study, plasma samples were collected from three groups of patients with CSCC, namely primary patients before treatment (BT group), patients with a poor prognosis (PP group, including patients with distant metastasis and local recurrence), and patients with a good prognosis within two years after the first treatment (GP group). The plasma metabolomics was conducted to detect the dynamic changes of metabolites via ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Multivariate analyses, including principle component, partial least square-discriminant, and orthogonal projection to latent structure-discriminant analyses, were performed to compare each pair of the three groups. The differential metabolites were identified by comparison of the exact m/z values and mass spectrometry (MS)/MS spectra with the structural information of the metabolites obtained from the Human Metabolome Database (http://www.hmdb.ca/) and LIPID MAPS (http://www.lipidmaps.org/). To screen for potential markers, receiver operating characteristic curve analysis of the differential metabolites. Finally, thirty plasma samples were collected from each group. Multivariate analyses showed that 31 metabolites were significantly different among the 3 groups studied. Of those, the 5 metabolites phosphatidyl choline (15:0/16:0), phosphatidyl glycerol (12:0/13:0), actosylceramide (d18:1/16:0), D-Maltose, and phthalic acid, with an area under the curve above 0.75, were identified as potential biomarkers. The present findings provide evidence for biomarkers to monitor prognosis of patients with CSCC, which may help in better managing the disease.