Identification and validation of a ferroptosis-related lncRNA signature to robustly predict the prognosis, immune microenvironment, and immunotherapy efficiency in patients with clear cell renal cell carcinoma

BACKGROUND: Ferroptosis is a new type of iron- and reactive oxygen species-dependent cell death, studies on ferroptosis-related long noncoding RNAs (FerLncRNAs) in clear cell renal cell carcinoma (ccRCC) are limited. The purpose of this study was to investigate the potential prognostic value of FerLncRNAs and their relationship with the immune microenvironment and immunotherapy response of ccRCC. METHODS: RNA sequencing data of 526 patients with ccRCC were downloaded from The Cancer Genome Atlas (TCGA) database. The patients with ccRCC in TCGA were randomly divided (1:1) into a training and testing cohort. ICGC and GEO databases were used for validation. Screening for FerLncRNAs was performed using Pearson’s correlation analysis with the reported ferroptosis-related genes. A FerLncRNA signature was constructed using univariate, LASSO, and multivariate Cox regression analyses in the training cohort. Internal and external datasets were performed to verify the FRlncRNA signature. Four major FRlncRNAs were verified through in vitro experiment. RESULTS: We identified seven FerLncRNAs (LINC00894, DUXAP8, LINC01426, PVT1, PELATON, LINC02609, and MYG1-AS1), and established a risk signature and nomogram for predicting the prognosis of ccRCC. Four major FRlncRNAs were verified with the prognosis of ccRCC in the GEPIA and K-M Plotter databases, and their expressions were validated by realtime PCR. The risk signature can also effectively reflect the immune environment, immunotherapy response and drug sensitivity of ccRCC. These FRlncRNAs have great significance to the implementation of individualized treatment and disease monitoring of ccRCC patients.