Identification and evaluation of circulating biomarkers for pancreatic cancer and their correlation with pancreatic stromal expression

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest of the common cancers, with a dismal prognosis attributed in part to late diagnosis in the majority of patients. Diagnosing early stage increases the likelihood of eligibility for surgical resection, currently the only available method of cure. In this thesis I have aimed to identify serum biomarkers for the diagnosis of PDAC, as a potential means of screening for the disease in a minimally-invasive manner. A glycoprotein (dubbed Liv1) was identified as a potential diagnostic biomarker in PDAC patient sera compared to patients with chronic pancreatitis (CP), a finding that was subsequently validated in an independent cohort of samples. As a benign inflammatory disease of the pancreas, pancreatitis commonly presents concurrently with PDAC making biomarkers that can distinguish the two a rarity. In attempting to identify the cause of increased circulating Liv1 in PDAC, in situ hybridisation performed on PDAC and CP tissue specimens identified tumour cells as a source of Liv1, producing and secreting the protein into the surrounding stroma. Tissue microarray (TMA) analysis revealed stromal Liv1 was more common in PDAC patients than in CP, consistent with ... (continues)