Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes

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.

Immunological and prognostic significance of novel ferroptosis-related genes in soft tissue sarcoma

“…Law et al suggested that HELLS mediated epigenetic silencing of various cancer suppressor genes and evidenced in hepatocellular carcinoma that its overexpression potentiated tumor cell migration and proliferation [ 41 ]. Huang et al identified high expression and prognostic impact of HELLS in STS samples [ 42 ], which also underpinned our findings. In the TCGA database of STS samples, GSEA indicated that NQO1 was closely connected to interleukin-related signaling pathways.…”

Identification of Ferroptosis-Related Genes as Biomarkers for Sarcoma

“…However, there is increasing evidence that iron poisoning plays an important role in neuro-diseases, including neurodegenerative diseases and cardiovascular diseases ( Zhou et al, 2020 ). In addition, a thorough FRG landscape analysis of soft tissue sarcoma revealed a new type of FRG related to cancer and prognosis ( Huang et al, 2021 ). Ferroptosis has recently become a treatment target and potential biomarkers for sarcoma ( Chen et al, 2021 ).…”

Identification and Validation of a Novel Pyroptosis-Related Gene Signature for Prognosis Prediction in Soft Tissue Sarcoma

“…Thus, GTEx including expression profiles of normal human tissues was the optimal data resource ( Carithers et al, 2015 ). The gene expression data of TCGA and GTEx were merged through sufficiently rigorous procedures ( Wang et al, 2018 ), and this novel method has been confirmed by several studies concerning TCGA-SARC cohort ( Hu et al, 2020 ; Huang et al, 2021 ). Besides, PRGs identified in this study showed good ability to distinguish STS from normal samples.…”