Sumit Sahni1, Christoph Krisp2, Mark P Molloy3, Christopher Nahm4, Sarah Maloney5, Josef Gillson4, Anthony J Gill6, Jaswinder Samra7, Anubhav Mittal8. 1. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia. Electronic address: sumit.sahni@sydney.edu.au. 2. Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia; Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics, University Medical Center Hamburg - Eppendorf, Hamburg, Germany. 3. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia; Bowel Cancer and Biomarker Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. 4. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia. 5. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Australia. 6. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; NSW Health Pathology, Dept of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. 7. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Australia. 8. Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Australia. Electronic address: anubhav.mittal@sydney.edu.au.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION AND GENERAL SIGNIFICANCE: A novel blood-based biomarker signature for PDAC prognosis was identified.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION AND GENERAL SIGNIFICANCE: A novel blood-based biomarker signature for PDAC prognosis was identified.
Authors: Sarah A Hendricks; Julie L King; Calvin L Duncan; Winston Vickers; Paul A Hohenlohe; Brian W Davis Journal: Genes (Basel) Date: 2022-08-22 Impact factor: 4.141