Abstract
BackgroundThe role of ferroptosis in tumorigenesis has been confirmed in previous studies. However, the comprehensive analysis of ferroptosis-related gene (FRG) to study the role of FRG in soft tissue sarcoma (STS) is lacking.MethodsRNA sequencing profile of TCGA-SARC cohort and GTEx were used to select differentially expressed FRGs (DEFRGs). Univariate, LASSO, and multivariate Cox analyses were selected to determine overall survival (OS)- and disease-free survival (PFS)-related FRGs. Two prognostic signatures were established and validated in two independent sets from Gene Expression Omnibus (GEO). Finally, the expression of key FRGs were validated with RT-qPCR.ResultsIn total, 198 FRGs (90.4%) were abnormally expressed in STS. Twelve DEFRGs were incorporated in the final signatures and showed favorable discrimination in both training and validation cohorts. Patients in the different risk groups not only showed different prognosis, but also showed different infiltration of immune cells. Two nomograms combining signature and clinical variables were established and the C-indexes were 0.852 and 0.752 for the OS and DFS nomograms, respectively. Finally, the expression of NOX5, HELLS, and RPL8 were validated with RT-qPCR.ConclusionThis comprehensive analysis of the FRG landscape in STS revealed novel FRGs related to carcinogenesis and prognosis. These findings have implications for prognosis and therapeutic responses, which revealed potential prognostic biomarkers and promote precision medicine.
Highlights
Ferroptosis, as a special kind of programmed cell death, is a process of cytological changes caused by the accumulation of iron-dependent lipid hydroperoxide [1]
In addition to study the prognosis of soft tissue sarcoma (STS) patients, we investigated that the relationship between ferroptosis-related gene (FRG) and the characteristics of immune cell infiltration in STS patients
Gene Ontology (GO) analysis suggested that differentially expressed FRGs (DEFRGs) were mainly enriched in response to oxidative stress, secondary lysosome, and cofactor binding in biological process, cellular component, and molecular function (Figure 1C)
Summary
Ferroptosis, as a special kind of programmed cell death, is a process of cytological changes caused by the accumulation of iron-dependent lipid hydroperoxide [1]. It is marked by the oxidative modification of phospholipid membranes, which is different from traditional apoptosis or autophagy cell death [1, 2]. In mice with intact p53, p53 binds to the SLC7A11 promoter region and inhibits its transcription, which is essential for the induction of ferroptosis [11] On this basis, the concept of the ferroptosis-related gene (FRG) was developed, which was closely associated with tumorigenesis. The expression of key FRGs were validated with RT-qPCR
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