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

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.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC6822243 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Zhu Yi Y Weiss Tobias T Zhang Qiushi Q Sun Rui R Wang Bo B Yi Xiao X Wu Zhicheng Z Gao Huanhuan H Cai Xue X Ruan Guan G Zhu Tiansheng T Xu Chao C Lou Sai S Yu Xiaoyan X Gillet Ludovic L Blattmann Peter P Saba Karim K Fankhauser Christian D CD Schmid Michael B MB Rutishauser Dorothea D Ljubicic Jelena J Christiansen Ailsa A Fritz Christine C Rupp Niels J NJ Poyet Cedric C Rushing Elisabeth E Weller Michael M Roth Patrick P Haralambieva Eugenia E Hofer Silvia S Chen Chen C Jochum Wolfram W Gao Xiaofei X Teng Xiaodong X Chen Lirong L Zhong Qing Q Wild Peter J PJ Aebersold Ruedi R Guo Tiannan T

Molecular oncology 20190918 11

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 o ...[more]

PMID: 31495056

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Project description:BackgroundThe surveillance and therapy of early-stage cancer would be better for patients' prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer.MethodsIn this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC).ResultsWe identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic.ConclusionWe disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.

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

Publications

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

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