Abstract 174P
Background
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival of <12%. Patients typically present with advanced disease. Developing a blood-based screening panel could offer a simple test without requiring invasive procedures, enabling earlier detection and accelerate drug discovery. This study integrated plasma-based proteomic, tissue and clinical data supported by the PURPLE pancreatic cancer registry to identify novel biomarkers that can aid screening for early-stage disease, predict survival outcomes and guide drug discovery.
Methods
Unbiased quantitative comparative proteomics analysis was performed via a 16-window diaPASEF method on a TIMS TOF Pro mass spectrometer. Data was searched with DIA-NN (v1.8.3) in library-free mode and normalisation using RUVIIIC (v1.0.19). Matched clinicopathological and survival data was extracted from the PURPLE pancreatic cancer registry.
Results
Proteomic analysis of plasma from 203 participants showed distinct protein changes between PDAC patients with early and late-disease stage. Plasma from 120 PDAC, 69 healthy controls and 14 alternative pancreatic pathologies were analysed. A total of 919 proteins were detected (mean of 400 in each sample). When comparing PDAC with healthy controls, 246 significant differentially expressed proteins were identified (false discovery rate, FDR <0.1). Hierarchical data clustering analysis demonstrated a clear protein signature of the top 40 differentially expressed proteins in PDAC. When comparing early versus late-stage PDAC, 12 significantly differentially expressed proteins were identified. Reactome pathway analysis revealed significant up-regulation in immune response and wound healing pathways, and down-regulation of lipid and glucose metabolism in PDAC. These findings suggest that abnormal processes are quantifiable and can be detected earlier in the blood.
Conclusions
A unique PDAC protein signature was identified when comparing PDAC to healthy controls and alternative pancreatic pathologies. The dysregulated proteins identified have potential therapeutic implications that could accelerate selection of drug targets, inform clinical trial design, and enable earlier blood-based PDAC screening.
Clinical trial identification
Australian New Zealand Clinical Trial Registy Trial Acronym: PURPLE Registry Pancreatic cancer: Understanding Routine Practice and Lifting End Results (PURPLE). A Prospective Pancreatic Cancer Clinical Registry Registration number: ACTRN12617001474347 Registered: 08/03/2017.
Editorial acknowledgement
Legal entity responsible for the study
Walter & Eliza Hall Institute.
Funding
Hemstritch Centenary Fellowship ( Awarded to Dr Belinda Lee), Philanthropic funding from the Hemstritch Foundation & Segal Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
571P - Dacomitinib in treatment-naïve EGFR-mutant NSCLC patients with multiple brain metastases: Initial efficacy and safety data from a phase II study
Presenter: Yongfeng Yu
Session: Poster Display
Resources:
Abstract
572P - Multivariable five-year survival prediction model for prognosing patients with EGFR-mutated NSCLC treated with EGFR-TKIs
Presenter: Qi-An Wang
Session: Poster Display
Resources:
Abstract
573P - LUMINATE-103: Real-world treatment patterns and outcomes of patients (pts) with epidermal growth factor receptor mutant (EGFR MU), non-squamous (NSQ) locally advanced/metastatic non-small cell lung cancer (a/mNSCLC): Pooled analysis of large US electronic health record (EHR) datasets
Presenter: Byoung Chul Cho
Session: Poster Display
Resources:
Abstract
574P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutations
Presenter: Lin Wu
Session: Poster Display
Resources:
Abstract
575P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC and brain metastasis: A multicenter cohort study
Presenter: Puyuan Xing
Session: Poster Display
Resources:
Abstract
576P - Clonality of both EGFR and co-occurring TP53 mutations affect the treatment efficacy of the third-generation EGFR-TKIs in advanced-stage EGFR-mutant non-small cell lung cancer
Presenter: Wen Feng Fang
Session: Poster Display
Resources:
Abstract
577P - A study of the efficacy and safety of amivantamab in EGFR exon 20 insertion (E20I) mutations in NSCLC
Presenter: Daeho Choi
Session: Poster Display
Resources:
Abstract
578P - Tyrosine kinase inhibitor treatment of elderly patients with epidermal growth factor receptor mutated advanced non-small cell lung cancer: A multi-institute retrospective study
Presenter: Ling-Jen Hung
Session: Poster Display
Resources:
Abstract
579P - Real-world study of dacomitinib as first-line treatment for patients with EGFR-mutant non-small cell lung cancer
Presenter: Ji Eun Shin
Session: Poster Display
Resources:
Abstract
580P - Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor <italic>(EGFR)</italic> 21L858R mutation: A multicenter, ambispective, consecutive case-series study
Presenter: Shouzheng Wang
Session: Poster Display
Resources:
Abstract