Beata Kuśnierz-Cabala1, Ewelina Nowak2, Mateusz Sporek3, Artur Kowalik2, Marek Kuźniewski4, Francisco J Enguita5, Ewa Stępień6. 1. Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. 2. Department of Molecular Diagnostics, Holycross Cancer Center, Kielce, Poland. 3. Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland; Surgery Department of the District Hospital in Sucha Beskidzka, Poland. 4. Department of Nephrology, Jagiellonian University Medical College, Krakow, Poland. 5. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. 6. Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland; Department of Medical Physics, M. Smoluchowski Institute of Physics, Jagiellonian University, Krakow, Poland. Electronic address: e.stepien@uj.edu.pl.
Abstract
OBJECTIVES: Vascular dysfunction is a severe complication which can cause organ ischemia and damage during acute pancreatitis (AP). Laboratory assessment of AP is based on several routine parameters and does not reflect endothelial dysfunction or organ injury. Recently, small non-protein-coding RNAs (miRNAs) have been introduced to laboratory diagnostics as new biomarkers or predictive parameters. Candidate miRNAs (hsa-miR-16-5p, -103a-3p, -122-5p, -126-5p, -148a-5p, -216a-5p, -375, and -551b-5b) were selected to check their possible clinical application in stratification of patients with different AP severity. METHODS: In this observational study, 62 patients with mild (MAP) and 26 with moderate and severe (SAP) acute pancreatitis were included. The control group consisted of 10 age and sex matched subjects. Circulating miRNAs were analyzed in serum using a quantitative real-time PCR method (q-RT-PCR) by means of 3'-locked-nucleic-acid primers. RESULTS: In SAP patients, a significant increase in most of the selected miRNAs (miR-126-5p, -148a-3p, -216a-5p and -551b-5p, and miR-375) was observed when compared to control subjects. In MAP patients, three miRNAs were significantly elevated: endothelial-specific miR-216a-5p, -551b-5p, as well as miR-375 that is highly abundant in pancreas. ROC analysis revealed that miR-126-p and miR-551b-5p can predict AP severity (AUC 0.748, sensitivity 60.0%, specificity 87.1%, p < 0.001) and (AUC 0.716; sensitivity 69.2%, specificity 72.6%, p < 0.001). miR-375 was not relevant (AUC 0.458; sensitivity 55.%, specificity 44.4%). CONCLUSIONS: A pancreatic miRNA signature can be useful for assessment of pancreatic injury in the acute phase of AP. Endothelial dysfunction during AP is reflected by levels of specific circulating miRNAs and may help in patient stratification.
OBJECTIVES:Vascular dysfunction is a severe complication which can cause organ ischemia and damage during acute pancreatitis (AP). Laboratory assessment of AP is based on several routine parameters and does not reflect endothelial dysfunction or organ injury. Recently, small non-protein-coding RNAs (miRNAs) have been introduced to laboratory diagnostics as new biomarkers or predictive parameters. Candidate miRNAs (hsa-miR-16-5p, -103a-3p, -122-5p, -126-5p, -148a-5p, -216a-5p, -375, and -551b-5b) were selected to check their possible clinical application in stratification of patients with different AP severity. METHODS: In this observational study, 62 patients with mild (MAP) and 26 with moderate and severe (SAP) acute pancreatitis were included. The control group consisted of 10 age and sex matched subjects. Circulating miRNAs were analyzed in serum using a quantitative real-time PCR method (q-RT-PCR) by means of 3'-locked-nucleic-acid primers. RESULTS: In SAPpatients, a significant increase in most of the selected miRNAs (miR-126-5p, -148a-3p, -216a-5p and -551b-5p, and miR-375) was observed when compared to control subjects. In MAP patients, three miRNAs were significantly elevated: endothelial-specific miR-216a-5p, -551b-5p, as well as miR-375 that is highly abundant in pancreas. ROC analysis revealed that miR-126-p and miR-551b-5p can predict AP severity (AUC 0.748, sensitivity 60.0%, specificity 87.1%, p < 0.001) and (AUC 0.716; sensitivity 69.2%, specificity 72.6%, p < 0.001). miR-375 was not relevant (AUC 0.458; sensitivity 55.%, specificity 44.4%). CONCLUSIONS: A pancreatic miRNA signature can be useful for assessment of pancreatic injury in the acute phase of AP. Endothelial dysfunction during AP is reflected by levels of specific circulating miRNAs and may help in patient stratification.