Key result
An integrative bioinformatics and text-mining approach identified a signature of 25 dysregulated genes that functionally connect steatosis progression to NASH and hepatocellular carcinoma.
Why the study?
While research studies on NASH progression are increasing, their findings are sometimes controversial, prompting a need to identify the most important and commonly described findings.
An integrative bioinformatics approach identified a 25-gene signature underlying the progression of NASH to hepatocellular carcinoma, providing potential new therapeutic targets.
Hypothesis-generating only; requires prospective validation before any clinical or research application.
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.
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Desterke et al. (2019) studied Nonalcoholic steatohepatitis (NASH). Dysregulated lipid-related genes was evaluated on Gene signature associated with NASH progression to HCC. An integrative bioinformatics and text-mining approach identified a signature of 25 dysregulated genes that functionally connect steatosis progression to NASH and hepatocellular carcinoma.
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