Frontiers in Oncology (Mar 2020)
Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy
- Sumit Sahni,
- Sumit Sahni,
- Sumit Sahni,
- Christopher Nahm,
- Christopher Nahm,
- Christopher Nahm,
- Christoph Krisp,
- Mark P. Molloy,
- Mark P. Molloy,
- Mark P. Molloy,
- Shreya Mehta,
- Shreya Mehta,
- Shreya Mehta,
- Sarah Maloney,
- Sarah Maloney,
- Malinda Itchins,
- Malinda Itchins,
- Malinda Itchins,
- Malinda Itchins,
- Nick Pavlakis,
- Nick Pavlakis,
- Nick Pavlakis,
- Nick Pavlakis,
- Stephen Clarke,
- Stephen Clarke,
- Stephen Clarke,
- Stephen Clarke,
- David Chan,
- David Chan,
- David Chan,
- David Chan,
- Anthony J. Gill,
- Anthony J. Gill,
- Viive M. Howell,
- Viive M. Howell,
- Jaswinder Samra,
- Jaswinder Samra,
- Jaswinder Samra,
- Anubhav Mittal,
- Anubhav Mittal,
- Anubhav Mittal
Affiliations
- Sumit Sahni
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Sumit Sahni
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Sumit Sahni
- Australian Pancreatic Centre, Sydney, NSW, Australia
- Christopher Nahm
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Christopher Nahm
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Christopher Nahm
- Australian Pancreatic Centre, Sydney, NSW, Australia
- Christoph Krisp
- Center for Diagnostics, Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg – Eppendorf, Hamburg, Germany
- Mark P. Molloy
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Mark P. Molloy
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
- Mark P. Molloy
- Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia
- Shreya Mehta
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Shreya Mehta
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Shreya Mehta
- Australian Pancreatic Centre, Sydney, NSW, Australia
- Sarah Maloney
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Sarah Maloney
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Malinda Itchins
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Malinda Itchins
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Malinda Itchins
- Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, NSW, Australia
- Malinda Itchins
- Northern Cancer Institute, St Leonards and Frenchs Forest, St Leonards, NSW, Australia
- Nick Pavlakis
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Nick Pavlakis
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Nick Pavlakis
- Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, NSW, Australia
- Nick Pavlakis
- Northern Cancer Institute, St Leonards and Frenchs Forest, St Leonards, NSW, Australia
- Stephen Clarke
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Stephen Clarke
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Stephen Clarke
- Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, NSW, Australia
- Stephen Clarke
- Northern Cancer Institute, St Leonards and Frenchs Forest, St Leonards, NSW, Australia
- David Chan
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- David Chan
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- David Chan
- Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, NSW, Australia
- David Chan
- Northern Cancer Institute, St Leonards and Frenchs Forest, St Leonards, NSW, Australia
- Anthony J. Gill
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Anthony J. Gill
- Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
- Viive M. Howell
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Viive M. Howell
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia
- Jaswinder Samra
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Jaswinder Samra
- Australian Pancreatic Centre, Sydney, NSW, Australia
- Jaswinder Samra
- 0Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, NSW, Australia
- Anubhav Mittal
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Anubhav Mittal
- Australian Pancreatic Centre, Sydney, NSW, Australia
- Anubhav Mittal
- 0Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, NSW, Australia
- DOI
- https://doi.org/10.3389/fonc.2020.00237
- Journal volume & issue
-
Vol. 10
Abstract
Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders.Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients.Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.
Keywords
