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Proteomic Characterization of Circulating Molecular Perturbations Associated With Pancreatic Adenocarcinoma Following Intravenous ω‐3 Fatty Acid and Gemcitabine Administration: A Pilot Study
Author(s) -
Runau Franscois,
Arshad Ali,
Isherwood John D.,
Sandhu Jatinderpal K.,
Ng Leong L.,
Dennison Ashley R.,
Jones Donald J. L.
Publication year - 2021
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1002/jpen.1952
Subject(s) - gemcitabine , pancreatic cancer , medicine , haptoglobin , adenocarcinoma , cancer , cancer research , oncology
Background : Administration of intravenous ω‐3 fatty acid (ω‐3FA) in advanced pancreatic adenocarcinoma patients receiving gemcitabine chemotherapy shows disease stabilization and improved progression‐free survival. Using high‐definition plasma proteomics, the underlying biological mechanisms responsible for these clinical effects are investigated. Methods and Results : A pilot study involving plasma that was collected at baseline from 13 patients with histologically confirmed, unresectable pancreatic adenocarcinoma (baseline group) after 1‐month treatment with intravenous gemcitabine and ω‐3FA (treatment group) and intravenous gemcitabine only (control group) and was prepared for proteomic analysis. A 2‐arm study comparing baseline vs treatment and treatment vs control was performed. Proteins were isolated from plasma with extensive immunodepletion, then digested and labeled with isobaric tandem mass tag peptide tags. Samples were then combined, fractionated, and injected into a QExactive‐Orbitrap Mass‐Spectrometer and analyzed on Proteome Discoverer and Scaffold with ensuing bioinformatics analysis. Selective reaction monitoring analysis was performed for verification. In total, 3476 proteins were identified. Anti‐inflammatory markers (C‐reactive protein, haptoglobin, and serum amyloid‐A1) were reduced in the treatment group. Enrichment analysis showed angiogenesis downregulation, complement immune systems upregulation, and epigenetic modifications on histones. Pathway analysis identified direct action via the Pi3K‐AKT pathway. Serum amyloid‐A1 significantly reduced ( P < .001) as a potential biomarker of efficacy for ω‐3FA. Conclusions : This pilot study demonstrates administration of ω‐3FA has potential anti‐inflammatory, antiangiogenic, and proapoptotic effects via direct interaction with cancer‐signaling pathways in patients with advanced pancreatic adenocarcinoma. Further studies in a larger sample size is required to validate the clinical correlation found in this preliminary study.