A Novel Prognostic Model Based on Ferroptosis-Related Gene Signature for Bladder Cancer

Abstract

BackgroundBladder cancer (BC) is a molecular heterogeneous malignant tumor; the treatment strategies for advanced-stage patients were limited. Therefore, it is vital for improving the clinical outcome of BC patients to identify key biomarkers affecting prognosis. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. Ferroptosis-related genes (FRGs) can be promising candidate biomarkers in BC. The objective of our study was to construct a prognostic model to improve the prognosis prediction of BC.MethodsThe mRNA expression profiles and corresponding clinical data of bladder urothelial carcinoma (BLCA) patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. FRGs were identified by downloading data from FerrDb. Differential analysis was performed to identify differentially expressed genes (DEGs) related to ferroptosis. Univariate and multivariate Cox regression analyses were conducted to establish a prognostic model in the TCGA cohort. BLCA patients from the GEO cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were used to explore underlying mechanisms.ResultsNine genes (ALB, BID, FADS2, FANCD2, IFNG, MIOX, PLIN4, SCD, and SLC2A3) were identified to construct a prognostic model. Patients were classified into high-risk and low-risk groups according to the signature-based risk score. Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) survival analysis confirmed the superior predictive performance of the novel survival model based on the nine-FRG signature. Multivariate Cox regression analyses showed that risk score was an independent risk factor associated with overall survival (OS). GO and KEGG enrichment analysis indicated that apart from ferroptosis-related pathways, immune-related pathways were significantly enriched. ssGSEA analysis indicated that the immune status was different between the two risk groups.ConclusionThe results of our study indicated that a novel prognostic model based on the nine-FRG signature can be used for prognostic prediction in BC patients. FRGs are potential prognostic biomarkers and therapeutic targets.

Upregulation of Ferroptosis-Related Fanconi Anemia Group D2 is a Poor Prognostic Factor and an Indicator of Tumor Immune Cell Infiltration in Lung Adenocarcinoma

“…A high level of FANCD2 expression upregulated the immune inhibitor expression of CTLA4, PDCD1, and LAG3 while downregulating immunostimulators, such as IL6R, TMEM173, TNFSF13, CD40LG, and HHLA2, which indicates that FANCD2 contributes to tumor immune escape by modulating the immunosuppressive microenvironment. This finding is consistent with previous studies ( Hong et al, 2021 ; Yang et al, 2021 ). Moreover, higher FANCD2 expression led to a remarkable reduction in the infiltration of CD8 + T cells, NK cells, and DC cells, but it also recruited Th2 cells, and it is closely connected to the corresponding marker genes of tumor infiltrates immune cells (TIICs) based on the ssGSEA, CIBERSORT, and GEPIA databases.…”

Upregulation of Ferroptosis-Related Fanconi Anemia Group D2 is a Poor Prognostic Factor and Indicator of Tumor Immune Cell Infiltration in Lung Adenocarcinoma

“…Moreover, FANCD2 plays an immunosuppressive role by downregulating immunostimulators, such asIL6R, TMEM173, TNFSF13, CD40LG, and HHLA2. Therefore, the results implied that FANCD2 contributes to tumor immune escape by modulating the immunosuppressive microenvironment, which was consistent with previous studies [35,36].…”

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

“…For example, a novel agent called AuNRs&IONs@Gel constructed by Pengyu Guo was reported to induce ferroptosis and trigger a potent immune response through a triple therapy strategy using FDA-approved nanoparticles in BLCA [ 39 ]. The relationship between immune statue and ferroptosis in BLCA has been explored by accumulating studies [ 40 , 41 ]. Luan et al found that immune cell infiltration and immune checkpoints in BLCA were dysregulated in BLCA patients with different levels of ferroptosis related genes using multiple experimental and bioinformatic models [ 41 ].…”