In Situ DESI-MSI Lipidomic Profiles of Breast Cancer Molecular Subtypes and Precursor Lesions

作者: Adriana Leandra Santoro , Rodrigo D. Drummond , Israel Tojal Silva , Severino S. Ferreira , Luiz Juliano

DOI: 10.1158/0008-5472.CAN-18-3574

关键词:

摘要: Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression these remain poorly understood. The recent development desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence analytical chemistry traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized composition cancer DESI-MSI. Regions interest were identified, including invasive (IBC), ductal carcinoma situ (DCIS), adjacent benign (ABT), metabolomic profiles at 200 μm elaborated using Biomap software Lasso method. Top ions identified IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, sphingolipids. Highly saturated lipids, as well antioxidant molecules [taurine (m/z 124.0068), uric acid 167.0210), ascorbic 175.0241), glutathione 306.0765)], able to distinguish from ABT. Moreover, luminal B triple-negative showed more complex lipid compared A HER2 subtypes. DCIS distinguished on basis cell signaling apoptosis-related [fatty acids (341.2100 382.3736 m/z) glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, PS (38:3), 812.5440)]. In summary, DESI-MSI distinct between across cancer, potential implications pathogenesis. SIGNIFICANCE: These findings present first four DCIS, normal tissue, add understanding their

参考文章(49)
Robert Tibshirani, Trevor Hastie, Daniela Witten, Gareth James, An Introduction to Statistical Learning: With Applications in R ,(2013)
Edward A. Dennis, Paul C. Norris, Eicosanoid storm in infection and inflammation Nature Reviews Immunology. ,vol. 15, pp. 511- 523 ,(2015) , 10.1038/NRI3859
Richard M. Weinshilboum, Diane M. Otterness, Ibrahim A. Aksoy, Thomas C. Wood, Chengtao Her, Rebecca B. Raftogianis, Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes. The FASEB Journal. ,vol. 11, pp. 3- 14 ,(1997) , 10.1096/FASEBJ.11.1.9034160
V A Fadok, D R Voelker, P M Henson, J J Cohen, P A Campbell, D L Bratton, Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. Journal of Immunology. ,vol. 148, pp. 2207- 2216 ,(1992)
Onno B. Bleijerveld, Martin Houweling, Michael J. Thomas, Zheng Cui, Metabolipidomics: profiling metabolism of glycerophospholipid species by stable isotopic precursors and tandem mass spectrometry. Analytical Biochemistry. ,vol. 352, pp. 1- 14 ,(2006) , 10.1016/J.AB.2006.02.016
Dirce M. Carraro, Eliana V. Elias, Victor P. Andrade, Ductal carcinoma in situ of the breast: morphological and molecular features implicated in progression. Bioscience Reports. ,vol. 34, pp. 19- 28 ,(2014) , 10.1042/BSR20130077
L. S. Eberlin, R. J. Tibshirani, J. Zhang, T. A. Longacre, G. J. Berry, D. B. Bingham, J. A. Norton, R. N. Zare, G. A. Poultsides, Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 111, pp. 2436- 2441 ,(2014) , 10.1073/PNAS.1400274111
L. S. Eberlin, M. Gabay, A. C. Fan, A. M. Gouw, R. J. Tibshirani, D. W. Felsher, R. N. Zare, Alteration of the lipid profile in lymphomas induced by MYC overexpression Proceedings of the National Academy of Sciences of the United States of America. ,vol. 111, pp. 10450- 10455 ,(2014) , 10.1073/PNAS.1409778111
Ralph J. DeBerardinis, Julian J. Lum, Georgia Hatzivassiliou, Craig B. Thompson, THE BIOLOGY OF CANCER: METABOLIC REPROGRAMMING FUELS CELL GROWTH AND PROLIFERATION Cell Metabolism. ,vol. 7, pp. 11- 20 ,(2008) , 10.1016/J.CMET.2007.10.002
Livia S. Eberlin, Christina R. Ferreira, Allison L. Dill, Demian R. Ifa, R. Graham Cooks, Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging. Biochimica et Biophysica Acta. ,vol. 1811, pp. 946- 960 ,(2011) , 10.1016/J.BBALIP.2011.05.006