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

ABSTRACT: 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.

SUBMITTER: Marien E

PROVIDER: S-EPMC4503522 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Marien Eyra E Meister Michael M Muley Thomas T Fieuws Steffen S Bordel Sergio S Derua Rita R Spraggins Jeffrey J Van de Plas Raf R Dehairs Jonas J Wouters Jens J Bagadi Muralidhararao M Dienemann Hendrik H Thomas Michael M Schnabel Philipp A PA Caprioli Richard M RM Waelkens Etienne E Swinnen Johannes V JV

International journal of cancer 20150407 7

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 ...[more]

PMID: 25784292

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Project description:BackgroundNon-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. The early detection of high-risk patients is essential to improve patient prognosis. Thus, the identification of a non-invasive, non-radiative, convenient, and fast diagnostic approach should be a top priority in NSCLC research. Circulating extracellular RNAs (exRNAs) in the plasma are potential biomarkers for NSCLC.MethodsWe used RNA-sequencing (RNA-seq) technology to explore the NSCLC-related RNAs, especially the circular RNAs (circRNAs). The circRNA-targeted micro RNAs (miRNAs) were predicted using 3 circRNA databases [i.e., the Cancer-Specific CircRNA Database (CSCD), circBank, and Circular RNA Interactome]. The circRNA-miRNA-messenger RNA (mRNA) network was constructed using Cytoscape V3.8.0 (Cytoscape Consortium, San Diego, CA, USA). The expression levels of some differentially expressed genes were validated by a quantitative real-time polymerase chain reaction (qRT-PCR) analysis.ResultsThe results showed that the RNA biotypes of the mitochondrial ribosomal RNAs (mt-rRNAs) and mitochondrial transfer RNAs (mt-tRNAs) were upregulated in the NSCLC plasma. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms of the differentially expressed transcripts of NSCLC included oxidative phosphorylation, proton transmembrane transport, and the response to oxidative stress. Additionally, the qRT-PCR validation indicated that hsa_circ_0000722 had significantly higher expression in the NSCLC plasma than the control plasma, but hsa_circ_0006156 did not differ between the NSCLC plasma and the control plasma. The expression levels of miR-324-5p and miR-326 were higher in the NSCLC plasma than the control plasma.ConclusionsIn this study, an exRNA-sequencing strategy was used to identify the expression of NSCLC-specific transcription factors in clinical plasma samples, and hsa_circ_0000722 and hsa-miR-324-5p were identified as potential biomarkers in NSCLC.

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

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

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