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Mol Oncol. 2019 Sep 8. doi: 10.1002/1878-0261.12570. [Epub ahead of print]

High-throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification.

Author information

1
Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
2
Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China.
3
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Switzerland.
4
Department of Neurology and Brain Tumor Center, University Hospital Zurich, University of Zurich, Switzerland.
5
Department of Pathology, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China.
6
College of Mathematics and Informatics, Digital Fujian Institute of Big Data Security Technology, Fujian Normal University, Fuzhou, China.
7
Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
8
Department of Pathology, The Second Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China.
9
Department of Urology, University Hospital Zurich, University of Zurich, Switzerland.
10
Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Switzerland.
11
Department of Neuropathology, University Hospital Zurich, University of Zurich, Switzerland.
12
Division of Medical Oncology, Lucerne Cantonal Hospital and Cancer Center, Switzerland.
13
Sciex, Shanghai, China.
14
Institute of Pathology, Cantonal Hospital St. Gallen, Switzerland.
15
Children's Medical Research Institute, University of Sydney, Australia.
16
Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany.
17
Faculty of Science, University of Zurich, Switzerland.

Abstract

Formalin-fixed, paraffin-embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)-SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B-cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh-frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.

KEYWORDS:

SWATH ; FFPE; biomarker; pressure cycling technology; proteome; tumor

PMID:
31495056
DOI:
10.1002/1878-0261.12570
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