Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study

• Published in: Journal of clinical medicine 2024-04, Vol.13 (8), p.2247
• Main Authors: Vilà-Quintana, Laura, Fort, Esther, Pardo, Laura, Albiol-Quer, Maria T, Ortiz, Maria Rosa, Capdevila, Montserrat, Feliu, Anna, Bahí, Anna, Llirós, Marc, Aguilar, Esther, García-Velasco, Adelaida, Ginestà, Mireia M, Laquente, Berta, Pozas, Débora, Lluansí, Aleix, Pimenoff, Ville Nikolai, Moreno, Victor, Garcia-Gil, Libadro Jesús, Duell, Eric J, Carreras-Torres, Robert, Aldeguer, Xavier
• Format: Article
• Language: English
• Subjects: Alcohol; Antioxidants; Biological markers; Biomarkers; Cancer therapies; Causality; Cytokines; Development and progression; Diagnosis; Disease; Enzymes; Ethylenediaminetetraacetic acid; Genetics; Growth factors; Health aspects; Homeostasis; Identification and classification; Inflammation; Lipid peroxidation; Lipids; Medical research; Medicine, Experimental; Oxidative stress; Pancreatic cancer; Pancreatitis; Pathogenesis; Patients; Permeability; Plasma; Risk factors; Serology; Superoxide; Variance analysis
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13082247

Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC ( = 12), CP ( = 21) and control subjects ( = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.