Dataset Information

Development and validation of ferroptosis-related lncRNAs prognosis signatures in kidney renal clear cell carcinoma

ABSTRACT:

Background

Ferroptosis is a recently recognised new type of cell death which may be a potential target for cancer therapy. In the present study, we aimed to screen ferroptosis-related differentially expressed long non-coding RNAs as biomarkers to predict the outcome of kidney renal clear cell carcinoma.

Methods

RNAseq count data and corresponding clinical information were obtained from the Cancer Genome Atlas database. Lists of ferroptosis-related genes and long non-coding RNAs were obtained from the FerrDb and GENCODE databases, respectively. The candidate prognostic signatures were screened by Cox regression analyses and least absolute shrinkage and selection operator analyses.

Results

Three ferroptosis-related long non-coding RNAs (DUXAP8, LINC02609, and LUCAT1) were significantly correlated with the overall survival of kidney renal clear cell carcinoma independently. Kidney renal clear cell carcinoma patients with high-risk values displayed worse OS. Meanwhile, the expression of these three ferroptosis-related long non-coding RNAs and their risk scores were significantly correlated with clinicopathological features. Principal component analyses showed that patients with kidney renal clear cell carcinoma have differential risk values were well distinguished by the three ferroptosis-related long non-coding RNAs.

Conclusions

The present study suggests that the risk assessment model constructed by these three ferroptosis-related long non-coding RNAs could accurately predict the outcome of kidney renal clear cell carcinoma. We also provide a novel perspective for cancer prognosis screening.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12935-021-02284-1.

SUBMITTER: Xing X

PROVIDER: S-EPMC8567554 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRecent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC).MethodsIn the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups.ResultsA 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups.ConclusionWe established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.