Metabolite Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a poor prognosis. This poor prognosis is largely attributed to a late-stage diagnosis. Recent advancements in metabolomics have emerged as a promising avenue for biomarker discovery in PDAC. This systematic review evaluates the potential of metabolite biomarkers for early detection of PDAC. Four studies meeting the inclusion criteria were analyzed, encompassing experimental, case-control, and prospective cohort designs. Key findings include the identification of distinct metabolic subtypes in PDAC with varying sensitivities to metabolic inhibitors. A biomarker signature comprising nine metabolites plus CA19-9 showed high accuracy in distinguishing PDAC from chronic pancreatitis, outperforming CA19-9 alone. Another study identified a five-metabolite signature demonstrating high diagnostic accuracy for pancreatic cancer, differentiating it from type 2 diabetes mellitus. A two-metabolite model (isoleucine and adrenic acid) showed superior performance in detecting stage-I PDAC compared to CA19-9. These studies consistently demonstrate altered metabolic pathways in PDAC patients compared to healthy controls and those with benign pancreatic conditions. Integrating metabolomic data with other molecular profiling approaches has become a powerful strategy for improving diagnostic accuracy. However, challenges remain, including the influence of confounding factors, the need for large-scale validation studies, and the standardization of metabolomic methods. The potential of artificial intelligence in interpreting complex metabolomic data offers promising avenues for future research. This review highlights the significant potential of metabolite biomarkers in early PDAC detection while emphasizing the need for further validation and refinement of these approaches.