A Novel Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

Int J Gen Med. 2022 Jan 6:15:207-222. doi: 10.2147/IJGM.S341034. eCollection 2022.

Abstract

Purpose: Papillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs can be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors.

Methods: Gene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso penalized Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed.

Results: We constructed a prognostic signature consisting of 15 ferroptosis-related lncRNAs. The K-M curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the lncRNA signature was 0.930, exhibiting robust prognostic capacity. The high-risk group had a greater degree of immune cell infiltration than the low-risk group. Significant differences in inflammation promotion, parainflammation, and type I IFN response were noted between the low-risk and high-risk groups (p < 0.01). The expression levels of immune checkpoints including CD80, IDO1, and LAG3 were significantly higher in the high-risk group than in the low-risk group (p < 0.05). Chemotherapy sensitivity analysis showed that MNX1-AS1, ZFAS1, MIR4435-2HG, and ADAMTS9-AS1 were significantly correlated with the sensitivity of some chemotherapy drugs (p < 0.05).

Conclusion: We demonstrated that a ferroptosis-related lncRNA prognostic signature could be a novel biomarker for PRCC.

Keywords: PRCC; ferroptosis; long non-coding RNA; prognostic signature.