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Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy.
Sahni, Sumit; Nahm, Christopher; Krisp, Christoph; Molloy, Mark P; Mehta, Shreya; Maloney, Sarah; Itchins, Malinda; Pavlakis, Nick; Clarke, Stephen; Chan, David; Gill, Anthony J; Howell, Viive M; Samra, Jaswinder; Mittal, Anubhav.
Affiliation
  • Sahni S; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
  • Nahm C; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia.
  • Krisp C; Australian Pancreatic Centre, Sydney, NSW, Australia.
  • Molloy MP; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
  • Mehta S; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia.
  • Maloney S; Australian Pancreatic Centre, Sydney, NSW, Australia.
  • Itchins M; Center for Diagnostics, Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg - Eppendorf, Hamburg, Germany.
  • Pavlakis N; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
  • Clarke S; Bowel Cancer and Biomarker Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia.
  • Chan D; Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia.
  • Gill AJ; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
  • Howell VM; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Camperdown, NSW, Australia.
  • Samra J; Australian Pancreatic Centre, Sydney, NSW, Australia.
  • Mittal A; Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.
Front Oncol ; 10: 237, 2020.
Article in En | MEDLINE | ID: mdl-32195182
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.
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Full text: 1 Database: MEDLINE Type of study: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Language: En Year: 2020 Type: Article
Fulltext
Print
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PubMed Links
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Full text: 1 Database: MEDLINE Type of study: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Language: En Year: 2020 Type: Article