Systematic analysis of the ABC transporter family in hepatocellular carcinoma reveals the importance of ABCB6 in regulating ferroptosis

Aims: ATP-binding cassette (ABC) transporters constitute one of the largest families of membrane proteins in most organisms; however, their functions in hepatocellular carcinoma (HCC) remain unclear. Main methods: A set of bioinformatic tools was integrated to analyze the expression of 49 members of the ABC transporter family. The function of members which had prognostic values in HCC was explored by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Key findings: ABCA8 and ABCA9 were significantly down-regulated in HCC. Prognostic analysis indicated that HCC patients with low expression of ABCA8 and ABCA9 had significantly shorter survival time. On the contrary, ABCB6 was over-expressed in the disease and high expression of ABCB6 was associated with worse prognosis. Co-expression analysis, and subsequently GO and KEGG analysis indicated that ABCA8 and ABCA9 might participate in the catabolic processes of multiple metabolites, while ABCB6 might regulate ferroptosis. Significance: This study reveals a previously unrecognized function of ABCB6 in HCC, by regulating ferroptosis. Since ABCB6 is over-expressed in HCC and ferroptosis involves in cancer development, ABCB6 might be a promising therapeutic target in the disease.