AUTHOR=Zhao Guo-Jiang , Wu Zonglong , Ge Liyuan , Yang Feilong , Hong Kai , Zhang Shudong , Ma Lulin 

TITLE=Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.650416

DOI=10.3389/fgene.2021.650416

ISSN=1664-8021

ABSTRACT=<p>Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Ferroptosis plays a vital role in ccRCC development and progression. We did an update of ferroptosis-related multigene expression signature for individualized prognosis prediction in patients with ccRCC. Differentially expressed ferroptosis-related genes in ccRCC and normal samples were screened using The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses and machine learning methods were employed to identify optimal prognosis-related genes. <italic>CARS1</italic>, <italic>CD44</italic>, <italic>FANCD2</italic>, <italic>HMGCR</italic>, <italic>NCOA4</italic>, <italic>SLC7A11</italic>, and <italic>ACACA</italic> were selected to establish a prognostic risk score model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly enriched in immune-related pathways; single-sample Gene Set Enrichment Analysis revealed several immune cells potentially related to ferroptosis. Kaplan–Meier survival analysis demonstrated that patients with high-risk scores had significantly poor overall survival (log-rank <italic>P</italic> = 7.815 × 10<sup>–11</sup>). The ferroptosis signature was identified as an independent prognostic factor. Finally, a prognostic nomogram, including the ferroptosis signature, age, histological grade, and stage status, was constructed. Analysis of The Cancer Genome Atlas-based calibration plots, C-index, and decision curve indicated the excellent predictive performance of the nomogram. The ferroptosis-related seven-gene risk score model is useful as a prognostic biomarker and suggests therapeutic targets for ccRCC. The prognostic nomogram may assist in individualized survival prediction and improve treatment strategies.</p>