PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 11; p. 129682
• Main Authors: Sahni, Sumit, Krisp, Christoph, Molloy, Mark P., Nahm, Christopher, Maloney, Sarah, Gillson, Josef, Gill, Anthony J., Samra, Jaswinder, Mittal, Anubhav
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2020
• Subjects: adenocarcinoma; Aged; biomarkers; Biomarkers, Tumor - blood; Carcinoma, Pancreatic Ductal - blood; Carcinoma, Pancreatic Ductal - diagnosis; Disease Progression; drug therapy; Female; Humans; Male; mass spectrometry; Microparticles; Middle Aged; neoplasm progression; Pancreatic ductal adenocarcinoma; pancreatic neoplasms; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - diagnosis; patients; Pilot Projects; Plasma; Prognosis; Prognostic biomarkers; Proteasome Endopeptidase Complex - blood; protein synthesis; protein-tyrosine-phosphatase; proteins; Proteomics; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - blood; Receptor-Like Protein Tyrosine Phosphatases, Class 3 - blood; relapse; resection; Retrospective Studies; statistical analysis; survival rate; Prognostic biomarkers; Plasma; Pancreatic ductal adenocarcinoma; Microparticles; Proteomics
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129682

Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Surgery is the only curative intent therapy, but the majority of patients experience disease relapse. Thus, patients who do not benefit from highly morbid surgical resection needs to be identified and offered palliative chemotherapy instead. In this pilot study, we aimed to identify differentially regulated proteins in plasma and plasma derived microparticles from PDAC patients with poor and good prognosis. Plasma and plasma derived microparticle samples were obtained before surgical resection from PDAC patients. Sequential Windowed Acquisition of all Theoretical fragment ion spectra – Mass Spectrometry (SWATH-MS) proteomic analysis was performed to identify and quantify proteins in these samples. Statistical analysis was performed to identify biomarkers for poor prognosis. A total of 482 and 1024 proteins were identified from plasma and microparticle samples, respectively, by SWATH-MS analysis. Statistical analysis of the data further identified nine and six differentially (log2ratio > 1, p < .05) expressed proteins in plasma and microparticles, respectively. Protein tyrosine phosphatases, PTPRM and PTPRB, were decreased in plasma of patients with poor PDAC prognosis, while proteasomal subunit PSMD11 was increased in microparticles of patients with poor prognosis. A novel blood-based biomarker signature for PDAC prognosis was identified. •SWATH-MS analysis of plasma and microparticles from PDAC patients was performed.•Microparticles provided deeper proteomic analysis compared to plasma.•Novel plasma and microparticle based prognostic biomarkers were identified.•PTPRM and PTPRB were decreased in plasma of PDAC patients with poor prognosis.•PSMD11 was increased in microparticles from PDAC patients with poor prognosis.