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

Abstract

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.

Discovery and Potential Functional Characterization of Long Noncoding RNAs Associated with Familial Acne Inversa with <i>NCSTN</i> Mutation

“…There may be two possible factors contributing to lncRNA expression differences. Firstly, inflammation may change lncRNAs expression in the skin lesions, which is supported by the present study, in which immune-related lncRNAs (ENST00000538665, named IFNG-AS1, ENST00000422459, named PELATON) [23,24] were also aberrantly expressed in AI patients. Secondly, other lncRNAs may be induced by defective expression of NCSTN.…”

Analysis of lncRNAs profiles associated with ferroptosis can predict prognosis and immune landscape and drug sensitivity in patients with clear cell renal cell carcinoma

“…Further investigation into these lncRNAs, particularly their roles in ferroptosis, could give new understanding that shed light on the molecular basis of ccRCC. [ 31 ] The prognostic effect of AP006545.1, AC105429.1, and LINC02348 on cancer is little understood. Therefore, more studies are required to analyze how FALs may affect the prognosis of ccRCC caused by ferroptosis.…”

“…Further investigation into these lncRNAs, particularly their roles in ferroptosis, could give new understanding that shed light on the molecular basis of ccRCC. [31] The prognostic effect of…”

Identification of disulfidptosis-related-ferroptosis associated lncRNAs signature as a novel prognosis model for kidney renal clear cell carcinoma

“…Several regulatory axes of lncRNAs have been identified that control the invasion and metastasis of ccRCC, such as CDKN2B-AS1/miR-141/CCND1 [29] and RP11-436H11.5/miR-335-5p/BCL-W [30]. Researchers have also investigated ferroptosis-related lncRNAs in ccRCC to identify new biomarkers and establish prognostic models [31]- [32] ,…”