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Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia

Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variati...

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Autores principales: Young, Reuben S. E., Claes, Britt S. R., Bowman, Andrew P., Williams, Elizabeth D., Shepherd, Benjamin, Perren, Aurel, Poad, Berwyck L. J., Ellis, Shane R., Heeren, Ron M. A., Sadowski, Martin C., Blanksby, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374165/
https://www.ncbi.nlm.nih.gov/pubmed/34421820
http://dx.doi.org/10.3389/fendo.2021.689600
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author Young, Reuben S. E.
Claes, Britt S. R.
Bowman, Andrew P.
Williams, Elizabeth D.
Shepherd, Benjamin
Perren, Aurel
Poad, Berwyck L. J.
Ellis, Shane R.
Heeren, Ron M. A.
Sadowski, Martin C.
Blanksby, Stephen J.
author_facet Young, Reuben S. E.
Claes, Britt S. R.
Bowman, Andrew P.
Williams, Elizabeth D.
Shepherd, Benjamin
Perren, Aurel
Poad, Berwyck L. J.
Ellis, Shane R.
Heeren, Ron M. A.
Sadowski, Martin C.
Blanksby, Stephen J.
author_sort Young, Reuben S. E.
collection PubMed
description Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of biomolecular markers. Comprising around 50% of cellular mass, and with known metabolic variations in cancer, lipids provide a promising target for molecular pathology. Here we apply isomer-resolved lipidomics in combination with imaging mass spectrometry to interrogate tissue sections from radical prostatectomy specimens. Guided by the histopathological assessment of adjacent tissue sections, regions of interest are investigated for molecular signatures associated with lipid metabolism, especially desaturation and elongation pathways. Monitoring one of the most abundant cellular membrane lipids within these tissues, phosphatidylcholine (PC) 34:1, high positive correlation was observed between the n-9 isomer (site of unsaturation 9-carbons from the methyl terminus) and epithelial cells from potential pre-malignant lesions, while the n-7 isomer abundance was observed to correlate with immune cell infiltration and inflammation. The correlation of lipid isomer signatures with human disease states in tissue suggests a future role for isomer-resolved mass spectrometry imaging in assisting pathologists with prostate cancer diagnoses and patient stratification.
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spelling pubmed-83741652021-08-20 Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia Young, Reuben S. E. Claes, Britt S. R. Bowman, Andrew P. Williams, Elizabeth D. Shepherd, Benjamin Perren, Aurel Poad, Berwyck L. J. Ellis, Shane R. Heeren, Ron M. A. Sadowski, Martin C. Blanksby, Stephen J. Front Endocrinol (Lausanne) Endocrinology Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of biomolecular markers. Comprising around 50% of cellular mass, and with known metabolic variations in cancer, lipids provide a promising target for molecular pathology. Here we apply isomer-resolved lipidomics in combination with imaging mass spectrometry to interrogate tissue sections from radical prostatectomy specimens. Guided by the histopathological assessment of adjacent tissue sections, regions of interest are investigated for molecular signatures associated with lipid metabolism, especially desaturation and elongation pathways. Monitoring one of the most abundant cellular membrane lipids within these tissues, phosphatidylcholine (PC) 34:1, high positive correlation was observed between the n-9 isomer (site of unsaturation 9-carbons from the methyl terminus) and epithelial cells from potential pre-malignant lesions, while the n-7 isomer abundance was observed to correlate with immune cell infiltration and inflammation. The correlation of lipid isomer signatures with human disease states in tissue suggests a future role for isomer-resolved mass spectrometry imaging in assisting pathologists with prostate cancer diagnoses and patient stratification. Frontiers Media S.A. 2021-08-05 /pmc/articles/PMC8374165/ /pubmed/34421820 http://dx.doi.org/10.3389/fendo.2021.689600 Text en Copyright © 2021 Young, Claes, Bowman, Williams, Shepherd, Perren, Poad, Ellis, Heeren, Sadowski and Blanksby https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Young, Reuben S. E.
Claes, Britt S. R.
Bowman, Andrew P.
Williams, Elizabeth D.
Shepherd, Benjamin
Perren, Aurel
Poad, Berwyck L. J.
Ellis, Shane R.
Heeren, Ron M. A.
Sadowski, Martin C.
Blanksby, Stephen J.
Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title_full Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title_fullStr Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title_full_unstemmed Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title_short Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia
title_sort isomer-resolved imaging of prostate cancer tissues reveals specific lipid unsaturation profiles associated with lymphocytes and abnormal prostate epithelia
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374165/
https://www.ncbi.nlm.nih.gov/pubmed/34421820
http://dx.doi.org/10.3389/fendo.2021.689600
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