Introduction: Pancreatic ductal adenocarcinoma (PDAC) is known as one of the deadliest cancer types. Its incidence rate shows almost parallel to the mortality rate, the global five-year survival rate has been estimated to range from 2% to 9%. PDAC is commonly found among elders aged over 60 years old, and the disease is most often at the advanced stage at diagnosis due to being asymptomatic. There are several risk factors that have been observed in common among patients with PDAC, such as diabetes mellitus, jaundice, and chronic pancreatitis. However, these symptoms do not serve as a clear indication to distinguish between pancreatic cancer patients and others. Since carbohydrate antigen 19-9 (CA 19-9) is the only tumour marker that is currently available for commercial use, more studies on potential diagnostic and prognostic biomarkers are needed for early diagnosis.
Objective: My project aimed to assess potential diagnostic and prognostic biomarkers by analysing metallomics in serum and tissue samples of patients with PDAC in comparison to sex- and age-matched healthy participants.
Methods: Serum samples were obtained from PDAC patients and the levels of ten essential and three toxic metals were measured in these samples using ICP-MS.
Results: Significantly decreased levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic and mercury were found, whereas molybdenum levels were increased. These significant changes were associated with PDAC diagnosis. When the levels of metals were characterised against the disease stage (I, II or III/IV), magnesium, potassium, iron and selenium concentrations were significantly decreased in all stages of PDAC patients compared to healthy controls. In contrast, a significant increase was found in molybdenum levels in stage II or III/IV patients when compared to healthy individuals. In a panel of lower levels of calcium, iron and selenium and higher levels of manganese demonstrated a significant association with poor prognosis in PDAC patients. Tissue metallomics in tumour tissues versus adjacent normal tissues also showed significantly increased levels of calcium, iron, zinc and selenium, whereas manganese and lead concentrations were significantly decreased. Significant changes in metal levels in tissue samples suggested an association with PDAC diagnosis.
Conclusion: Metallomics in both serum and tissue samples of PDAC patients demonstrated potential diagnostic and prognostic ability compared to healthy controls.