Published online Mar 18, 2017. doi: 10.4254/wjh.v9.i8.443
Peer-review started: October 17, 2016
First decision: November 14, 2016
Revised: November 29, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: March 18, 2017
To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies.
Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.
We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome. However some pathways were regulated in opposite directions in ALD and NAFLD, for example, glycolysis was down-regulated in ALD and up-regulated in NAFLD. Interestingly, we found rate-limiting genes such as HMGCR, SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD (down-regulated) and NAFLD (up-regulated). We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE. Additionally, we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.
Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile. Thus, it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile - also as possible drug targets. The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
Core tip: With a meta-analysis of newly published liver biopsy-derived transcriptome datasets we identified multiple key genes and pathways in common and mutually exclusive in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). We provide a compendium of comparative regulation for all KEGG pathways in both diseases and propose a list of biomarkers distinguishing both diseases. One surprising finding was that cholesterol metabolism was up-regulated in NAFLD and down-regulated in ALD although leading to the same steatosis phenotype which might be explained by an insufficient conversion rate to bile acids under both conditions.