A Reliable Biomarker Derived from Plasmalogens to Evaluate Malignancy and Metastatic Capacity of Human Cancers

Abstract

Antigen tumor markers employed in monitoring therapeutical approaches are limited by their specificity (Sp) and sensitivity (Se). The aim of this study was to investigate the suitability of a lipid tumor marker derived from ether-linked phospholipids and to compare it with others usually assayed in clinical practice. Complex lipids from normal and pathological breast, lung, and prostate tissue were isolated and analyzed by TLC and c-GLC methods. Results were compared as pooled samples, or by means of the averaged percent changes with respect to the composition observed in the normal tissue of the same patient. Sp, Se, negative-predictive (NPV) and positive- predictive values (PPV) were established for conventional markers and for the proposed lipid-derived marker. Results demonstrated that the content of monoenoic fatty acyl chains was significantly increased in total lipids, phosphatidylethanolamine, and especially in ethanolamine-containing ether lipids of neoplastic tissues with respect to their corresponding normal ones. Major changes were observed in the plasmalogen sub-fraction where the ratio monoenoic/saturated fatty acids can distinguish with high Se normal tissues from either benign or neoplastic tissues from breast, lung, or prostate lesions. Analyses of fatty acyl chains from ethanolamine-containing plasmalogens provided a reliable tumor marker that correlated with high Se and linearity with metastases spreading. This fact may be useful in prognosis of the most frequently observed human cancers.

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

“…Importantly, previous publications demonstrated that the analysis of lipid extracts obtained from tumor human cells lines or human cancer biopsies showed increased levels of PC and/or PE ether lipids. In fact, these changes are correlated with malignancy and metastatic potential in various cancers [37][38][39][40][41][42]. Some studies demonstrated that plasmalogens are natural antioxidants, as the ether link is more prone to be oxidized than the double bonds usually found in many phospholipids in their fatty acid moiety [9,43].…”

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

“…There is evidence for the involvement of oxylipins (Poczobutt et al 2006) and phospholipid species (Tyurina et al 2011) in tumour development from animal models of lung cancer. This is supported by clinical studies showing altered profiles of various lipids in plasma of lung cancer patients, including lysophospholipids (Dong et al 2010;Guo et al 2012), free fatty acids (Liu et al 2014), sphingomyelins, plasmalogens, phosphoglycerides and related lipids (Smith et al 2008;De Castro et al 2008;Ma et al 2011). Lipid profiling or lipidomics is an emerging field within metabolomics which focuses on monitoring changes in biofluid profiles of lipids and factors that interact with lipids.…”

“…The lipid biomarkers which contributed most to differentiate between adenocarcinoma and squamous carcinoma were phospholipids, triglycerides and sphingomyelins (Table 4) Alzheimer's disease and metastatic cancer (Brites et al 2004, Smith et al 2008). …”

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

“…Ether-linked GPLs affect membrane fl uidity and are associated with several cellular dysfunctions and malignancies. The presence of these lipid species is typically correlated to metastatic properties of human cancers ( 67 ) and may be involved in the intrahepatic metastasis of HCC.…”