Identification of alcoholic associated hepatitis-related genes and mesenchymal stem cell treatment target genes by meta analysis

초록

Background and aims: Alcoholic associated hepatitis (AH) is a lifethreatening condition and widespread chronic liver condition that places patients at risk of short-term mortality if it is not properly managed. This study aimed to identify transcriptomic biomarkers and cell therapy targets for AH. Method: We conduct a systematic meta-analysis of published human gene expression studies on liver biopsies and blood derived gene data. First, three liver AH transcriptome datasets and a blood AH dataset were combined to discover a common phenotype. Second, two AH prognosis datasets were compiled, which are including gene phenotype reflecting prognosis. Using inverse weighted variancebased method mounted in METAL software, the candidate genes related to AH in liver and blood tissues and annotated them as the liver-blood AH meta genes. Third, three MSC datasets were curated for gene identification in stem cell response. Meta-analysis was implemented on the individual cohort-specific summary statistics obtained from differential expression methods to identify the AHrelated biomarkers. To narrow down the candidate hub genes among stem cell treated data, TF database, protein-protein interaction network, disease-gene association database, and disease- and expression-related SNP database were used to analysis. Results: With previously identified alcoholic gene-related databases, external verification was performed and 47 upstream AH-related genes were presented. The analysis contains some genes that have not been previously characterized in the context of alcoholic liver disease. Conclusion: We present key genes involved in the progression of AH and provide a meta-analysis of results in a objective, statisticallybased format. And at the same time, we suggest this biomarkers that can predict the prognosis of AH and treatment response. By using these genes, we can confirm the genetic changes caused by stem cell treatment and this can be used to lay the foundation for targeted cell therapy or function-enhanced genetic therapy.