Non‐small cell lung cancer is characterized by dramatic changes in phospholipid profiles
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.
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Tài liệu tham khảo
Globocan.In: Cancer IAfRo ed. 2012.Available at:http://globocan.iarc.fr/. (Accessed on: Sept 30 2014).
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.
KislukJ CiborowskiM NiemiraM et al.Proteomics biomarkers for non‐small cell lung cancer.J Pharm Biomed Anal2014;101:40‐9.
Visca P, 2004, Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma, Anticancer Res, 24, 4169
EberlinLS GabayM FanAC et al.Alteration of the lipid profile in lymphomas induced by MYC overexpression.Proc Natl Acad Sci USA2014;111:10450–55.
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.