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Open AccessArticle

Lipid Related Genes Altered in NASH Connect Inflammation in Liver Pathogenesis Progression to HCC: A Canonical Pathway

1
Inserm, UMR-S 935, Université Paris Sud, F-94800 Villejuif, France
2
Laboratoire Croissance, Régénération, Réparation et Régénération Tissulaires (CRRET)/ EAC CNRS 7149, Univ Paris-Est Créteil (UPEC), F-94010 Créteil, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5594; https://doi.org/10.3390/ijms20225594
Received: 9 October 2019 / Revised: 3 November 2019 / Accepted: 4 November 2019 / Published: 8 November 2019
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
Nonalcoholic steatohepatitis (NASH) is becoming a public health problem worldwide. While the number of research studies on NASH progression rises every year, sometime their findings are controversial. To identify the most important and commonly described findings related to NASH progression, we used an original bioinformatics, integrative, text-mining approach that combines PubMed database querying and available gene expression omnibus dataset. We have identified a signature of 25 genes that are commonly found to be dysregulated during steatosis progression to NASH and cancer. These genes are implicated in lipid metabolism, insulin resistance, inflammation, and cancer. They are functionally connected, forming the basis necessary for steatosis progression to NASH and further progression to hepatocellular carcinoma (HCC). We also show that five of the identified genes have genome alterations present in HCC patients. The patients with these genes associated to genome alteration are associated with a poor prognosis. In conclusion, using an integrative literature- and data-mining approach, we have identified and described a canonical pathway underlying progression of NASH. Other parameters (e.g., polymorphisms) can be added to this pathway that also contribute to the progression of the disease to cancer. This work improved our understanding of the molecular basis of NASH progression and will help to develop new therapeutic approaches. View Full-Text
Keywords: NAFLD; NASH; canonical pathway; text-mining; lipids; inflammation NAFLD; NASH; canonical pathway; text-mining; lipids; inflammation
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Desterke, C.; Chiappini, F. Lipid Related Genes Altered in NASH Connect Inflammation in Liver Pathogenesis Progression to HCC: A Canonical Pathway. Int. J. Mol. Sci. 2019, 20, 5594.

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