A Novel Predictive Model for Adrenocortical Carcinoma Based on Hypoxia- and Ferroptosis-Related Gene Expression.

Background: The impact of hypoxia on ferroptosis is important in cancer proliferation, but no predictive model combining hypoxia and ferroptosis for adrenocortical carcinoma (ACC) has been reported. The purpose of this study was to construct a predictive model based on hypoxia- and ferroptosis-related gene expression in ACC. Methods: We assessed hypoxia- and ferroptosis-related gene expression using data from 79 patients with ACC in The Cancer Genome Atlas (TCGA). Then, a predictive model was constructed to stratify patient survival using least absolute contraction and selection operation regression. Gene expression profiles of patients with ACC in the Gene Expression Omnibus (GEO) database were used to verify the predictive model. Results: Based on hypoxia-related gene expression, 79 patients with ACC in the TCGA database were divided into three molecular subtypes (C1, C2, and C3) with different clinical outcomes. Patients with the C3 subtype had the shortest survival. Ferroptosis-related genes exhibited distinct expression patterns in the three subtypes. A predictive model combining hypoxia- and ferroptosis-related gene expression was constructed. A nomogram was constructed using age, sex, tumor stage, and the predictive gene model. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the gene signature was mainly related to the cell cycle and organelle fission. Conclusion: This hypoxia-and ferroptosis-related gene signature displayed excellent predictive performance for ACC and could serve as an emerging source of novel therapeutic targets in ACC.