Bioinformatics analysis of ferroptosis-relatedgenes in hepatocellular carcinoma

Introduction: Hepatocellular carcinoma (HCC) is the fourthdeadliest cancer worldwide. ferroptosis is a novel iron-dependentregulated cell death pathway shown to be involved in cancerand other diseases. In this study, we used Transcriptome analysisto obtain significant prognostic genes to meet the need forimproved clinical diagnosis.Materials and Methods: In this study, the microarray datasetGSE۱۳۶۲۴۷ was obtained from the Gene Expression Omnibus(GEO) database. The tumors were compared to healthy samplesafter normalization to identify differentially expressedgenes (DEGs) using the Transcriptome analysis console (TAC)with cut-off values of p-Value < ۰.۰۵ and |logFC| ≥ ۲. Geneontology was carried out using Enrichr, while the Ferroptosisgene list was obtained from Ferrdb. A Multiple List Comparator(https://molbiotools.com/listcompare.php) was used to identifycommon genes between the HCC DEGs and ferroptosis genes.A protein-protein interaction network (PPI) was created usingSTRING and hub genes were acquired using Cytoscape.Results: Results showed ۲۵۰ upregulated and ۸۲۱ downregulatedgenes from ۱۰۷۱ DEGs. Prominently, upregulated geneswere involved in pathways of ECM-receptor interaction, Cellcycle, PI۳K-Akt signaling, Hematopoietic cell lineage, andferroptosis. Down-regulated genes were involved in the pathwaysof cytochrome P۴۵۰ xenobiotics Metabolism, Drug metabolism Retinol metabolism, Fatty acid degradation, and bilesecretion. Furthermore, a comparison between HCC DEGs andferroptosis genes showed ۳۸ common genes. Interestingly, ۵ferroptosis-related genes (i.e., GOT۱, AURKA, CP, HELLS,and SCP۲) were among HCC hub genes. In addition to ferroptosis,these genes were involved in primary bile acid biosynthesis,Progesterone-mediated oocyte maturation, and phenylalanine,tyrosine, and tryptophan biosynthesis.Conclusion: Our analyses identified ferroptosis as an importantpathway involved in HCC development. it seems that inductionof ferroptosis might potentially be a new strategy tocontrol HCC development and progression. More in silico andexperimental studies are required to confirm our findings.

کلیدواژه ها:

Hepatocellular carcinoma ، ferroptosis ، differentiallyexpressed gene ، transcriptome analysis ، hub genes