Identification of mRNA and lncRNA profiles and potential targeted agents for fibrolamellar carcinoma based on RNA-sequencing data

Abstract

Abstract Background: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or virus infections. Patients with FLC often have non-specific symptoms and are often diagnosed at a later stage with a higher frequency of metastases compared to other liver cancers. A fusion transcript of DNAJB1 and PRKACA has been identified in all FLC patients, which can lead to increased activity of PKA and cellular proliferation, although the exact mechanism through which FLC develops remains unclear. In this study, we investigated common mRNA and lncRNA profiles in various FLC samples using bioinformatics analysis. Methods: We analyzed differentially expressed mRNAs and lncRNAs from three different public datasets. We performed Gene Ontology (GO), KEGG, and Protein-Protein Interaction (PPI) Network analyses with the differentially expressed (DE) mRNAs of FLC. Using DE mRNAs and lncRNAs, we predicted potential lncRNA target genes and screened for small molecule compounds for the FLC. Results: We identified 912 differentially expressed mRNAs and 308 differentially expressed lncRNAs from RNA sequencing analysis. GO analysis showed that the upregulated mRNAs in FLC were enriched in collagen fibril and extracellular matrix organization, while the downregulated mRNAs were enriched in xenobiotic metabolic and exogenous drug catabolic process. Furthermore, the upregulated mRNAs were enriched in PI3k-Akt signaling pathway based on KEGG pathway analysis, and in epithelial mesenchymal transition from GSEA analysis. we performed trans-target prediction analysis and identified 454 co-expressed pairs in FLC. Lastly, we screened and obtained potential therapeutic small molecule compounds using hub genes of FLC we identified. Conclusions: Our study revealed common mRNA and lncRNA expression profiles in FLC, and identified hub genes of DE mRNAs and lncRNA target genes, as well as small molecular compounds that could potentially be used as treatments. These results could contribute to further understanding of FLC and provides potential avenues for diagnosis and treatment.