Identification and validation of a novel prognostic signature based on ferroptosis-related genes in Ovarian Cancer

Background: Ovarian cancer (OC) is the most lethal gynecological tumor, which has a poor prognosis due to lack of early symptoms, resistance to chemotherapy, and recurrence. Ferroptosis belongs to regulated cell death family, which is characterized by iron-dependent process and is associated with cancer formation and treatment. Here, comprehensive bioinformatics analysis was applied to explore a valuable prognostic model based on ferroptosis-related genes, which was further validated in clinical OC samples. Methods mRNA data of normal and ovarian tumor samples were achieved from GTEx and TCGA databases separately. The ferroptosis genes expression pattern was analyzed and the prognostic clinical information was combined with gene expression data in normal and tumor tissues. Intersectional genes that were both differentially expressed and prognosis-related were found. A gene model based on ferroptosis-associated genes was established and evaluated in the common datasets. Finally, prognostic efficiency of the model was assessed in the clinical tissues of OC patients. Results A gene signature consisting of ALOX12, RB1, DNAJB6, STEAP3, and SELENOS was constructed. The signature divided TCGA, ICGC, and GEO cohorts into high-risk and low-risk groups separately, and the overall survival curves in all three cohorts had significant differences. Receiver operating characteristic (ROC) curves and independent prognostic factor analysis were carried out to show the risk model possessing good prognostic function, which was associated with several immune-related pathways. Moreover, protein expression and prognostic value of ALOX12 were validated in clinical samples of OC patients. Conclusion This work built and assessed a novel ferroptosis-associated gene model. Further, the clinical predictive role of ALOX12 was identified in OC patients, which suggested that ALOX12 might act as a potential prognostic tool and therapeutic target for OC patients.