A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma

Abstract

Background: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM. Methods: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan–Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan–Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment. Results: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan–Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature. Conclusions: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.

An Original Ferroptosis-Related Gene Signature Effectively Predicts the Prognosis and Clinical Status for Colorectal Cancer Patients

“…( 20 – 23 ). Recently, there are studies exploring the prognostic value of ferroptosis-related gene signature from public databases in several tumors, including uveal melanoma, lung cancer, hepatocellular carcinoma, pancreatic cancer, and glioma ( 15 , 24 – 28 ). However, there are still few scientific and clinical studies on the correlation between CRC and ferroptosis, whether ferroptosis is correlated with CRC prognosis, and identification of the key ferroptosis-related genes in CRC progression remains largely unknown.…”

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma

“…Meanwhile, the differential expression analysis and univariate Cox analysis were firstly constructed to screen these genes, which might also help to discover more specific prognostic markers to screen for innovative treatment targets. Like signatures associated with immune checkpoint (Tian et al, 2020), lncRNAs (Liu et al, 2019), ferroptosis (Luo & Ma, 2021), and hypoxia (Shou et al, 2020), our risk signature also had high predictive accuracy for the OS of patients with CM. We also analyzed whether immune status, tumor microenvironment, immune components, tumor stemness, and chemotherapeutic drug sensitivity corresponded to the gene signature and pyroptosis genes, and found that our risk signature conferred advantages compared with those described above.…”

miR-3587 Targets HMOX1 to Attenuate Ferroptotic Renal Injury Following Ischemia-Reperfusion

“…It is worth noting that, on the one hand, the present study only screened the cDEGs of IR_3h and IR_24h, in order to screen the early genetic changes of IR. On the other hand, with reference to other research methods [17,18], the present study used external validation datasets which utilized different rat models, all of which exhibited comparable HMOX1 expression trends across these diverse sample types. In addition, this study was the rst to report the use of miRNAs targeting HMOX1 to regulate ferroptotic injury in a renal IR model system.…”