Relative Ratios Enhance the Diagnostic Power of Phospholipids in Distinguishing Benign and Cancerous Ovarian Masses.

Tsukasa Yagi,Cyrus E Kuschner,Annette T Lee,Lance B Becker,Muhammad Shoaib,Junhwan Kim,Rishabh C Choudhary

doi:10.3390/cancers12010072

Abstract

Ovarian cancer remains a highly lethal disease due to its late clinical presentation and lack of reliable early biomarkers. Protein-based diagnostic markers have presented limitations in identifying ovarian cancer. We tested the potential of phospholipids as markers of ovarian cancer by utilizing inter-related regulation of phospholipids, a unique property that allows the use of ratios between phospholipid species for quantitation. High-performance liquid chromatography mass spectrometry was used to measure phospholipid, lysophospholipid, and sphingophospholipid content in plasma from patients with benign ovarian masses, patients with ovarian cancer, and controls. We applied both absolute and relative phospholipid ratios for quantitation. Receiver operating characteristic analysis was performed to test the sensitivity and specificity. We found that utilization of ratios between phospholipid species greatly outperformed absolute quantitation in the identification of ovarian cancer. Of the phospholipids analyzed, species in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) were found to have great biomarker potential. LPC(20:4)/LPC(18:0) carried the greatest capacity to differentiate cancer from control, SM(d18:1/24:1)/SM(d18:1/22:0) to differentiate benign from cancer, and PC(18:0/20:4)/PC(18:0/18:1) to differentiate benign from control. These results demonstrate the potential of plasma phospholipids as a novel marker of ovarian cancer by utilizing the unique characteristics of phospholipids to further enhance the diagnostic power.

Highlights

Ovarian cancer has the highest mortality among gynecological cancers despite remarkable advances in the knowledge of molecular biology and treatment [1,2]
We investigate the use of global lipidomics to identify phospholipid biomarkers with the potential to distinguish control, benign, and cancerous ovarian conditions
PC plasmalogens (PCP) species account for only a minor portion of PC

Summary

Introduction

Ovarian cancer has the highest mortality among gynecological cancers despite remarkable advances in the knowledge of molecular biology and treatment [1,2] These poor outcomes are attributable to the lack of early presenting symptoms or reliable biomarkers, which limit physicians’. Represents the principle ovarian cancer biomarker; while it carries utility in assessing for cancer resurgence or tracking chemotherapy efficacy, it represents a poor screening tool, detecting approximately 50% of patients with stage I ovarian cancer. This marker alone is not recommended to distinguish between benign and malignant adnexal masses [3,4]. The diagnosis of benign or malignant adnexal mass requires histopathologic examination of a surgically removed tumor [2]

Methods

Results

Conclusion