title: From moderately severe to severe hypertriglyceridemia induced acute pancreatitis: circulating miRNAs play role as potential biomarkers.
abstract: The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for evaluating the progression of HTAP, miRNAs showed good AUC. These data suggested that serum miRNAs have the potential to be excellent HTAP biomarkers.
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Fangmei
authors.initials: F
authors.lastname: An
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Mindan
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000097:blood; D016000:Cluster Analysis; D019295:Computational Biology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D010195:Pancreatitis / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D016207:Cytokines; C540193:MIrn181 microRNA, human; D035683:MicroRNAs