Abstract

Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy worldwide due to its high recurrence rate after surgery and chemotherapy. There is a critical need for discovery of novel biomarkers for EOC recurrence providing higher prediction power than that of the present ones. Lipids have been reported to associate with development and progression of cancer. In the current study, we aim to identify and validate the lipids which were relevant to the ovarian cancer recurrence based on plasma lipidomics performed by ultra-performance liquid chromatography coupled with mass spectrometry. In order to fulfill this objective, plasma from 70 EOC patients with follow up information was obtained. The results revealed that patients with and without recurrence could be clearly distinguished based on their lipid profiles. Thirty-one lipid metabolites were identified as potential biomarkers for EOC recurrence. The AUC value of these metabolite combinations for predicting EOC recurrence was 0.897. In terms of clinical applicability, LysoPG(20:5) arose as a potential EOC recurrence predictive biomarker to increase the predictive power of clinical predictors from AUC value 0.739 to 0.875. Additionally, we still found that individuals with early relapses (< 6 months) had a distinctive metabolomic pattern compared with late EOC and non-EOC recurrence subjects. Interestingly, decreased levels of triglycerides (TGs) were found to be a specific metabolic feature foreshadowing an early relapse. In conclusion, plasma lipidomics study could be used for predicting EOC recurrences, as well as early and late recurrent cases. The lipid biomarker research improves the predictive power of clinical predictors and the identified biomarkers are of great prognostic and therapeutic potential.

Highlights

  • Epithelial ovarian cancer (EOC) is the most fatal gynecologic malignancy worldwide

  • We aim to identify and validate the lipids which were relevant to the ovarian cancer recurrence based on plasma lipidomics performed by ultra-performance liquid chromatography coupled with mass spectrometry

  • We still found that individuals with early relapses (< 6 months) had a distinctive metabolomic pattern compared with late EOC and non-EOC recurrence subjects

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Summary

Introduction

Epithelial ovarian cancer (EOC) is the most fatal gynecologic malignancy worldwide. Approximately204,000 new EOC cases are diagnosed each year, of which 125,000 women would die annually [1]. Despite ongoing progress in cytoreductive surgery and high initial chemotherapy sensitivity, more than 60% of patients with advanced stages will still relapse within five years after treatment. These patients are rarely curable and have a 5-year overall survival rate of 25–35% [4, 5]. There is a great need for discovering effective and accessible predictive markers for EOC recurrence. Such biomarkers would facilitate implementation of both second-line chemotherapy and molecular targeted therapy

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