Identification of serum protein biomarkers for pre-cancerous lesions associated with Pancreatic Ductal Adenocarcinoma (Part3:Human)

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis as early-stage asymptomaticity leads to late-stage diagnoses. Strategies to detect PDAC earlier or identify predisposed individuals are therefore paramount. Here we report results from genetically engineered mice (GEMMs) and PDAC patients that identify serum proteins associated with pancreatic intraepithelial neoplasms (PanINs) (the most common PDAC precursor) and early-stage PDAC. Initially we screened previously described PanIN-abundant GEMMs, harbouring Pdx1-Cre, Lox-STOP-Lox-KrasG12D/+ and floxed alleles of essential autophagy genes Atg7-/- or Atg5-/-. Serum from these mice was assessed by proteomics and hits compared to those identified in KrasG12D/+ Trp53R172H/+ Pdx1-Cre (KPC) mice (which closely recapitulate human disease) and early-stage (I-II) PDAC patients. Inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) was elevated in all three screens, with complement C5, complement factors B and H, and CD14 increased in KPC mice and PDAC patients; all significantly increase co-ordinately in PDAC, with each elevating with disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with confidence, and when combined with additional screening could help increase survival from this significant disease.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Sergio Lilla  

LAB HEAD: Kevin Ryan

PROVIDER: PXD065581 | Pride | 2026-06-15

REPOSITORIES: Pride