Key Ferroptosis Genes and their Predictive and Diagnostic Value in Fanconi Anemia

Fanconi anemia (FA) and ferroptosis both affect tumor-related processes. However, few studies have reported on genetic associations between FA and ferroptosis. Our study evaluated the usefulness of genes related to ferroptosis in predicting and diagnosing FA. Transcriptome sequencing data were collected from 11 normal participants and 21 patients with FA. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) analysis, gene correlation analysis, protein-protein interaction network analysis, qRT-PCR, and pan-cancer analysis were performed. The pan-cancer analysis was carried out based on data obtained from the GTEx and TCGA databases. Two hundred ninety-eight differentially expressed genes were detected based on the comparison of FA patients and normal participants, among which four critical non-FA genes, MAD2L1, ASPM, PCNA, and TOP2A, were identified. Among the ferroptosis-related genes, five genes, including CDKN1A, EMC2, FDFT1, HSPB1, and MT1G, were identified as being associated with FA, and the areas under the curve (AUC) of these five ferroptosis-related genes were 0.907, 0.640, 0.902, 0.840, and 0.929, respectively. The AUC for the diagnosis of FA reached 1.000 when the five ferroptosis-related genes were used in combination. In addition, the expressions of CDKN1A, EMC2, FDFT1, and HSPB1 were associated with the prognosis of multiple cancers (P<0.05). The five ferroptosis-related genes CDKN1A, EMC2, FDFT1, HSPB1, and MT1G exhibited excellent predictive effects for the diagnosis of FA.