A Prognostic Signature for Clear Cell Renal Cell Carcinoma Based on Ferroptosis-Related lncRNAs and Immune Checkpoints

Abstract

Background: Ferroptosis is a potential target for cancer therapy, and lncRNAs can also affect ferroptosis by regulating related genes. The pathogenesis of clear cell renal cell carcinoma (ccRCC) regarding the regulation of ferroptosis by lncRNAs is still unknown.Methods: We constructed a risk model based on data in ccRCC patients obtained from the TCGA database and validated the diagnostic and prognostic value of the model. In addition, immune function and immune checkpoint variability analysis validated the association of ferroptosis with ccRCC tumor immunity.Results: The characteristics of ferroptosis-related lncRNAs (FRLs) were significantly correlated with the prognosis of ccRCC patients. The prognostic characteristics of FRLs were independent prognostic factors in ccRCC patients. Gene function in the high-risk group was associated with oxygen metabolic processes and immune pathways. Immune checkpoint variability analysis showed that HAVCR2, NRP1, and HHLA2 were upregulated in the low-risk group, while CD44, TNFRSF18, TNFSF14, TNFRSF8, CD276, and TNFRSF25 were upregulated in the high-risk group.Conclusions: The prognostic characteristics of FRLs can effectively predict the prognosis of ccRCC patients and provide a new direction for clinical treatment.

Identification and Validation of a Novel Ferroptotic Prognostic Genes-Based Signature of Clear Cell Renal Cell Carcinoma

“…Based on the five databases, a signature including nine genes was employed to predict outcomes of ccRCC patients. Except MT1G and CA9, the other seven genes of the signature were not involved in previous signatures [16,18,19,46,[49][50][51], which might be attributed to using a fragmentary gene set. Therefore, the nine-gene signature in this study could be more successful at distinguishing high-risk and low-risk patients and more accurate in predicting the prognosis of patients.…”

“…A great number of genes, long non-coding RNAs (lncRNAs), and compounds have been studied and explored by researchers and different mechanisms have been reported. Different gene-or lncRNA-based signatures have been explored and pos-sess prognostic value [18,19,[45][46][47]. Prognostic models are fundamental to developing a personalized therapy, moreover, an early diagnosis is of paramount importance in these cases [48].…”

Targeting ferroptosis in renal cell carcinoma: Potential mechanisms and novel therapeutics

“…These ferroptosis-related lncRNAs play an important role in the immune environment, immunotherapy response, and drug sensitivity of RCC, which helps to determine the individualized prognosis and treatment for RCC patients [ 71 , 72 ]. Dong et al also established a ferroptosis-related lncRNA model that could accurately predict the prognosis of RCC, which is associated with oxygen metabolic processes and immune microenvironment [ 73 ]. Further analysis revealed that these prognostic models may regulate RCC immune function via modulating several key pathways, such as the P53 and tumor necrosis factor-mediated signaling pathway, which further affects stage, grade, and survival outcomes of RCC [ 74 ].…”