Molecular Characterization of Prostate Cancer with Associated Gleason Score Using Mass Spectrometry Imaging.


Journal

Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042

Informations de publication

Date de publication:
05 2019
Historique:
received: 28 09 2018
revised: 19 12 2018
accepted: 06 02 2019
pubmed: 13 2 2019
medline: 29 4 2020
entrez: 13 2 2019
Statut: ppublish

Résumé

Diagnosis of prostate cancer is based on histologic evaluation of tumor architecture using a system known as the "Gleason score." This diagnostic paradigm, while the standard of care, is time-consuming, shows intraobserver variability, and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in regions of tissue that appeared histologically benign, possibly suggestive of precancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols, and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support image-guided prostate biopsy. IMPLICATIONS: In this study, we suggest that metabolomic differences between prostate cancers with different Gleason scores can be detected by mass spectrometry imaging.

Identifiants

pubmed: 30745465
pii: 1541-7786.MCR-18-1057
doi: 10.1158/1541-7786.MCR-18-1057
pmc: PMC6497547
mid: NIHMS1521525
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1155-1165

Subventions

Organisme : NCI NIH HHS
ID : R01 CA201469
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007627
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015898
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA089017
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD087211
Pays : United States

Informations de copyright

©2019 American Association for Cancer Research.

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Auteurs

Elizabeth C Randall (EC)

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Giorgia Zadra (G)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Paolo Chetta (P)

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
University of Milan, Milan, Italy.

Begona G C Lopez (BGC)

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Sudeepa Syamala (S)

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Sankha S Basu (SS)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Jeffrey N Agar (JN)

Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts.

Massimo Loda (M)

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Clare M Tempany (CM)

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Fiona M Fennessy (FM)

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Nathalie Y R Agar (NYR)

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Nathalie_Agar@dfci.harvard.edu.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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