Serum miR-4488 as a Potential Biomarker of Lean Nonalcoholic Fatty Liver Disease

Abstract In lean individuals, NAFLD is not a benign disease,and these patients have longterm morbidity and mortality similar to those of their nonlean counterparts.It is urgent to find biomarkers for noninvasive and early detection. miRNAs are useful biomarkers for detection.The aims of this study were to investigate the potential role of serum miRNAs in the detection of lean NAFLD and to explore the possible pathogenesis of lean NAFLD.Here, a total of 498 patients with NAFLD and 98 healthy controls were included to compare the clinical characteristics of lean NAFLD patients(BMI < 23 kg/m2),nonlean NAFLD patients(BMI ≥ 23kg/m2) and normal healthy individuals.A total of fourteen serum samples were collected for high-throughput profiling to identify altered miRNA expression patterns in lean NAFLD.The candidate miRNA miR-4488 was identified by filtering based on studies in a second independent cohort(31LNs,62NLNs and 72HIs) that included qRT-PCR analysis.GO enrichment, KEGG enrichment, and PPI network analyses were performed to investigate the potential molecular mechanism of miR-4488 in lean NAFLD. miR-4488 was selected as the candidate biomarker for lean NAFLD. The serum level of miR-4488 was increased in LNs compared to HIs(P < 0.0001) and to NLNs(P = 0.025).miR-4488 had acceptable performance in predicting[area under the curve(AUC) = 0.794,0.698]lean NAFLD. Moreover,GO and KEGG enrichment analyses revealed that the differentially expressed target genes were mainly involved in choline metabolism in cancer, the TNF signaling pathway and the p53 signaling pathway.PPI analysis identified ARHGAP1, SLC10A1 and SIX5 as the hub genes.Taken together, our findings indicate that serum miR-4488 is a potential biomarker for diagnosing and predicting the pathogenetic mechanisms of lean NAFLD.