From Moderately Severe to Severe Hypertriglyceridemia Induced Acute Pancreatitis: Circulating MiRNAs Play Role as Potential Biomarkers

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高甘油三酯血症性急性胰腺炎（hypertriglyceridemia induced acute pancreatitis, HTAP）在中国的发病率持续上升。该病伴有全身并发症且病死率较高，因此对该疾病严重程度开展早期评估的重要性愈发凸显。循环微RNA（microRNAs, miRNAs）有望成为判断疾病进展的新型非侵入性生物标志物。本研究旨在明确血清miRNAs作为HTAP进展新型生物标志物的潜在价值。本研究将HTAP患者分为中度重症组（moderately severe HTAP, HTMSAP）与重症组（severe HTAP, HTSAP），并以健康人群作为对照组。通过微阵列芯片（microarray）检测三组人群的血清miRNA表达谱，再采用实时荧光定量PCR（quantitative real-time PCR, qRT-PCR）进行验证。利用生物信息学分析对差异表达miRNAs的靶基因进行功能与通路富集预测，并构建miRNA-mRNA调控网络。此外，本研究还探究了miR-181a-5p与胰腺炎代谢相关物质的相关性，同时分别检测了中度重症急性胰腺炎（moderately severe acute pancreatitis, MSAP）与重症急性胰腺炎（severe acute pancreatitis, SAP）患者不同时间点的血清炎症细胞因子及miRNA浓度。最后对miRNAs的受试者工作特征（receiver operating characteristic, ROC）曲线展开分析。HTAP患者血清中下述miRNAs的浓度存在显著变化（P