Transcriptomics Identify Thrombospondin-2 as a Biomarker for NASH and Advanced Liver Fibrosis.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Kazuhiro KozumiTetsuo Takehara

Abstract

NAFLD is the most common liver disease worldwide. NASH, the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers. Global RNA sequencing of liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and patients with NASH exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins up-regulated in NASH and/or advanced fibrosis (stage F3-F4), including matricellular glycoprotein thrombospondin-2 (TSP-2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune...Continue Reading

References

May 29, 1999·Gastroenterology·C A MatteoniA J McCullough
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Jun 9, 2005·Gastroenterology·Vlad RatziuUNKNOWN LIDO Study Group
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Jul 9, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ariel E FeldsteinArthur J McCullough
Aug 31, 2011·Cold Spring Harbor Perspectives in Biology·Josephine C Adams, Jack Lawler
Aug 6, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cynthia A MoylanAnna Mae Diehl
Oct 4, 2016·Cellular and Molecular Life Sciences : CMLS·Yao Yao
Oct 6, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Martin L DecarisRohit Loomba
Feb 12, 2017·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Ki M Mak, Rena Mei
May 13, 2017·Science·Peter J ThulEmma Lundberg
Jan 19, 2018·Methods in Molecular Biology·Binbin ChenAsh A Alizadeh
Jul 7, 2018·Journal of the Endocrine Society·Glenn S GerhardJohanna K DiStefano
Oct 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Takahiro KodamaNeal G Copeland
Jan 18, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Malte P SuppliFilip K Knop
Mar 29, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Wei ChenHong You
May 23, 2019·Nature Reviews. Gastroenterology & Hepatology·Laurence P Diggs, Tim F Greten
Feb 12, 2020·Gastroenterology·Robert F SchwabeUtpal B Pajvani
Feb 18, 2020·Gastroenterology·Thomas G Cotter, Mary Rinella
Oct 13, 2020·Contemporary Clinical Trials·Timothy HardyUNKNOWN LITMUS Consortium
Nov 1, 2020·Nature Reviews. Gastroenterology & Hepatology·Tatiana Kisseleva, David Brenner
Jan 3, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Takefumi KimuraTakeji Umemura

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Jul 25, 2021·International Journal of Molecular Sciences·Chunye Zhang, Ming Yang

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