LncPRYP4-3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by
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ORIGINAL ARTICLE
LncPRYP4‑3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by targeting RPS4Y2 Hongju Yang1 · Qian Li2 · Leisheng Zhang3,4 · Mei Zhu1 · Jie Niu5 · Fenglin Xue1 · Lihong Yang6 · Qiu Qu1 · Yaling Lao1 · Zheng Ding1 · Changyan Xiao1 · Kunhua Wang1 Received: 15 February 2020 / Accepted: 23 May 2020 © Springer Nature Switzerland AG 2020
Abstract Longitudinal studies have improved current diagnostics and management of metabolic associated fatty liver disease (MAFLD) patients by liver biopsy and therapeutic intervention, yet the deficiency of biomarker spectrum for dissecting subtypes largely hinders the symptomatic treatment. We originally enriched serum from peripheral blood of 618 healthy donors (HD) and 580 MAFLD (400 NAFL, 180 NASH) patients according to multiple clinicopathological indicators. Microarray profiling and qRT-PCR were conducted to identify lncRNAs as candidate biomarkers of MAFLD. Then, we analyzed the matching score of the indicated lncRNA with CAP or MAFLD-associated pathological parameters as well. Additionally, we took advantage of interaction network together with gene expression profiling analysis to further explore the underlying target genes of the identified lncRNA. Herein, we found CAP in nearly all of the NAFL (399/400) and NASH (179/180) patients was higher than that in the HDs (611/618). The differentially expressed lncRNAs were involved in multiple metabolic or immunologic processes by regulating MAFLD-associated pathways. Of them, serum lncPRYP4-3 was identified as a novel candidate biomarker of MAFLD, which was further confirmed by correlation analysis with clinical indicators. Thereafter, we deduced PRS4Y2 was a candidate target of lncPRYP4-3 and mediated the dysfunction in NAFL and NASH patients. Serum lncPRYP4-3 served as a novel biomarker of MAFLD and helped distinguish the subtypes and benefit precise intervention therapy. Our findings also provided overwhelming new evidence for the alteration in biological processes and gene ontology in MAFLD patients. Keywords MAFLD · NAFL · NASH · lncPRYP4-3 · PRS4Y2 Abbreviations CAP Controlled attenuation parameter LSM Liver stiffness measurement ALT Alanine aminotransferase Hongju Yang, Qian Li, Leisheng Zhang those authors contributed equally to this work Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10238-020-00636-1) contains supplementary material, which is available to authorized users. * Hongju Yang [email protected] * Leisheng Zhang [email protected] * Kunhua Wang [email protected] Extended author information available on the last page of the article
AST Aspartate aminotransferase BMI Body mass index BUN Blood urea nitrogen GGT γ-Glutamyl transferase ALP Alkaline phosphatase TB Total bilirubin LDL-C Low-density lipoprotein-cholesterol HDL-C High-density lipoprotein-cholesterol TG Triglyceride TC Total cholesterol SUA Serum uric acid PChE Pseudocholinesterase PLT Platelet count F
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