Non‐small cell lung cancer is characterized by dramatic changes in phospholipid profiles

International Journal of Cancer - Tập 137 Số 7 - Trang 1539-1548 - 2015
Eyra Marien1, Michael Meister2,3, Thomas Muley2,3, Steffen Fieuws4, Sergio Bordel5, Rita Derua6, Jeffrey M. Spraggins7, Raf Van de Plas8,7, Jonas Dehairs1, Jens Wouters1, Muralidhararao Bagadi1, Hendrik Dienemann9,2, Michael Thomas10,2, Philipp A. Schnabel2,11, Richard M. Caprioli7, Etienne Waelkens6, Johannes V. Swinnen1
1Department of Oncology Laboratory of Lipid Metabolism and Cancer, KU Leuven—University of Leuven Leuven Belgium
2TLRC‐H – Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research Heidelberg Germany
3Thoraxklinik at University Hospital Heidelberg, Translational Research Unit, Heidelberg, Germany
4Department of Public Health and Primary Care I‐Biostat KU Leuven—University of Leuven and Universiteit Hasselt Leuven Belgium
5Department of Chemical and Biological Engineering, Systems Biology Group, Chalmers University of Technology, Gothenburg, Sweden
6Department of Cellular and Molecular Medicine Laboratory of Protein Phosphorylation and Proteomics, KU Leuven – University of Leuven Leuven Belgium
7Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN
8Delft University of Technology, Delft Center for Systems and Control, CD Delft, The Netherlands
9Department of Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
10Department of Thoracic Oncology Thoraxklinik at University Hospital Heidelberg Heidelberg Germany
11University Hospital Heidelberg, Institute of Pathology, Heidelberg, Germany

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Globocan.In: Cancer IAfRo ed. 2012.Available at:http://globocan.iarc.fr/. (Accessed on: Sept 30 2014).

10.1186/1755-8794-7-15

TanDS Camilleri‐BroetS TanEH et al.Intertumor heterogeneity of non‐small‐cell lung carcinomas revealed by multiplexed mutation profiling and integrative genomics.Int J Cancer2014;135:1092‐100.

10.1186/1755-8794-6-53

10.1177/153303461000900201

10.1089/omi.2010.0088

KislukJ CiborowskiM NiemiraM et al.Proteomics biomarkers for non‐small cell lung cancer.J Pharm Biomed Anal2014;101:40‐9.

10.1038/nature13419

10.1158/0008-5472.CAN-09-3871

10.1016/S0006-291X(03)00265-1

10.1038/nrc2222

10.1016/j.biochi.2010.03.019

10.1093/carcin/bgq131

Visca P, 2004, Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma, Anticancer Res, 24, 4169

10.1038/cddis.2013.444

10.1021/ac970888i

10.1016/j.jasms.2007.06.010

10.1111/j.2517-6161.1995.tb02031.x

10.1177/0272989X09360067

10.1089/omi.2013.0175

10.1371/journal.pone.0048889

10.1158/0008-5472.CAN-10-3894

10.1016/j.bcp.2014.05.011

EberlinLS GabayM FanAC et al.Alteration of the lipid profile in lymphomas induced by MYC overexpression.Proc Natl Acad Sci USA2014;111:10450–55.

10.1007/s10238-001-8020-5

10.1038/nature11404

10.1016/0885-4505(92)90041-V

10.1073/pnas.1115484108

10.1093/jn/124.5.615

10.1016/j.abb.2003.08.023

10.1006/bbrc.2000.2178

DoriaML RibeiroAS WangJ et al.Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival.Faseb J2014;28:4247–64.

10.1016/j.lungcan.2011.10.016

10.1126/scitranslmed.3005623

Thông tin
Thông tin xuất bản

International Journal of Cancer

Tập 137 Số 7

1539-1548

Thông tin tác giả