Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
Artikel i vetenskaplig tidskrift, 2015

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.

phospholipids

lipidomics

mass spectrometry

2D-imaging MS

non-small cell lung cancer

Författare

E. Marien

KU Leuven

M. Meister

Member of the German Center for Lung Research

Universitatsklinikum Heidelberg

T. Muley

Universitatsklinikum Heidelberg

Member of the German Center for Lung Research

S. Fieuws

KU Leuven

Sergio Velasco

Chalmers, Biologi och bioteknik, Systembiologi

R. Derua

KU Leuven

J. Spraggins

Vanderbilt University Medical Center

R. Van de Plas

Technische Universiteit Delft

Vanderbilt University Medical Center

J. Dehairs

KU Leuven

J. Wouters

KU Leuven

M. Bagadi

KU Leuven

H. Dienemann

Member of the German Center for Lung Research

Universitatsklinikum Heidelberg

M. Thomas

Member of the German Center for Lung Research

Universitatsklinikum Heidelberg

P. A. Schnabel

Universitatsklinikum Heidelberg

Member of the German Center for Lung Research

R. M. Caprioli

Vanderbilt University Medical Center

E. Waelkens

KU Leuven

J. V. Swinnen

KU Leuven

International Journal of Cancer

0020-7136 (ISSN) 1097-0215 (eISSN)

Vol. 137 1539-1548

Ämneskategorier

Cancer och onkologi

DOI

10.1002/ijc.29517

PubMed

25784292