Phospholipase D2: A biomarker implicated in various pancreatic diseases beyond acute pancreatitis

Abstract

Acute pancreatitis (AP) remains a clinical challenge due to its heterogeneous presentation and potential for rapid progression to severe disease. In their editorial, Wang et al highlight phospholipase D2 (PLD2) as a novel candidate biomarker, proposing its involvement in key inflammatory pathways and its inverse correlation with disease severity. While this represents a promising improvement in precision diagnostics, significant gaps remain that require further investigation. Specifically, the functional role of PLD2 in the molecular cascade of AP is not yet fully understood. Questions still remain, such as: Is the observed downregulation of PLD2 a causal factor or an epiphenomenon? Does PLD2 modulation offer a tangible therapeutic benefit beyond a mere correlation? These questions highlight the necessity of mechanistic in vivo studies to validate the role and therapeutic potential of PLD2. Furthermore, interindividual variability in inflammatory responses raises concerns regarding PLD2’s predictive consistency across genetically diverse populations. The temporal dynamics of PLD2 expression in AP also remain unclear; establishing whether its variations precede clinical deterioration is essential for its use in early risk stratification, integrating multiomics research (proteomics, metabolomics, transcriptomics, and lipidomics), which can clarify the biological interactions and regulatory pathways of PLD2 under complex mechanisms. Likewise, well-designed, multicenter, prospective studies will be essential in determining its true clinical value. The research by Wang et al initiates an intriguing direction in the quest for AP biomarkers, but further research is required before PLD2 can be established as a clinically applicable tool. Additional efforts are required to close this gap and define whether its role transcends a mere association in order for it to become a therapeutic target.

Keywords: Phospholipase D2; Acute pancreatitis; Chronic pancreatitis; Pancreatic Biomarkers; Pancreatic cancer; Sexual dimorphism

Core Tip: Phospholipase D2 is a key enzyme involved in the hydrolysis of phospholipids. It has been implicated in processes, such as neutrophil migration, the inflammatory response, apoptosis, cell migration, and adhesion in various pathologies. This letter to the editor analyzes multiple research sources on phospholipase D2 in pancreatic conditions, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer. It also highlights the need for future research to consider sex differences in the expression of this enzyme and to evaluate its applicability in clinical practice.