Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue

Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fo...

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Autores principales:	Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	non-small cell lung carcinoma lipidomics Fourier-transform mass spectrometry SMIRFE Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/71d7cd8c2dff47edba9bb2a5e5e4c12f
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spelling	oai:doaj.org-article:71d7cd8c2dff47edba9bb2a5e5e4c12f2021-11-25T18:20:34ZUntargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue10.3390/metabo111107402218-1989https://doaj.org/article/71d7cd8c2dff47edba9bb2a5e5e4c12f2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/740https://doaj.org/toc/2218-1989Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, high abundance and high m/z sphingolipid, and low abundance glycerophospholipid metabolic phenotype across the NSCLC samples. At the class level, higher abundances of sterol esters and lower abundances of cardiolipins were observed suggesting altered stearoyl-CoA desaturase 1 (SCD1) or acetyl-CoA acetyltransferase (ACAT1) activity and altered human cardiolipin synthase 1 or lysocardiolipin acyltransferase activity respectively, the latter of which is known to confer apoptotic resistance. The presence of a shared metabolic phenotype across a variety of genetically distinct NSCLC subtypes suggests that this phenotype is necessary for NSCLC development and may result from multiple distinct genetic lesions. Thus, targeting the shared affected pathways may be beneficial for a variety of genetically distinct NSCLC subtypes.Joshua M. MitchellRobert M. FlightHunter N. B. MoseleyMDPI AGarticlenon-small cell lung carcinomalipidomicsFourier-transform mass spectrometrySMIRFEMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 740, p 740 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung carcinoma lipidomics Fourier-transform mass spectrometry SMIRFE Microbiology QR1-502
spellingShingle	non-small cell lung carcinoma lipidomics Fourier-transform mass spectrometry SMIRFE Microbiology QR1-502 Joshua M. Mitchell Robert M. Flight Hunter N. B. Moseley Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
description	Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, high abundance and high m/z sphingolipid, and low abundance glycerophospholipid metabolic phenotype across the NSCLC samples. At the class level, higher abundances of sterol esters and lower abundances of cardiolipins were observed suggesting altered stearoyl-CoA desaturase 1 (SCD1) or acetyl-CoA acetyltransferase (ACAT1) activity and altered human cardiolipin synthase 1 or lysocardiolipin acyltransferase activity respectively, the latter of which is known to confer apoptotic resistance. The presence of a shared metabolic phenotype across a variety of genetically distinct NSCLC subtypes suggests that this phenotype is necessary for NSCLC development and may result from multiple distinct genetic lesions. Thus, targeting the shared affected pathways may be beneficial for a variety of genetically distinct NSCLC subtypes.
format	article
author	Joshua M. Mitchell Robert M. Flight Hunter N. B. Moseley
author_facet	Joshua M. Mitchell Robert M. Flight Hunter N. B. Moseley
author_sort	Joshua M. Mitchell
title	Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
title_short	Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
title_full	Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
title_fullStr	Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
title_full_unstemmed	Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue
title_sort	untargeted lipidomics of non-small cell lung carcinoma demonstrates differentially abundant lipid classes in cancer vs. non-cancer tissue
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/71d7cd8c2dff47edba9bb2a5e5e4c12f
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Untargeted Lipidomics of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes in Cancer vs. Non-Cancer Tissue

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