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Research Paper|Volume 13, Issue 15|pp 19789—19804

Comprehensive analysis of new prognostic signature based on ferroptosis-related genes in clear cell renal cell carcinoma

Bin Zheng1,2,3, Zhihong Niu1,2,3, Shubin Si4, Guiting Zhao2,3, Jianwei Wang5, Zhongshun Yao2,3, Fajuan Cheng6,7, Wei He2,3
  • 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
  • 2Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
  • 3Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
  • 4Department of Urology, People's Hospital of Yiyuan County, Zibo, Shandong, China
  • 5Department of Urology, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong, China
  • 6Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
  • 7Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
* Equal contribution
Received: May 5, 2021Accepted: July 15, 2021Published: August 9, 2021
https://doi.org/10.18632/aging.203390

Copyright: © 2021 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor and the most common subtype of RCC. Ferroptosis is a novel form of regulated cell death, and ferroptosis-related genes (FRGs) have been associated with the prognosis of patients with certain cancers. However, the detailed prognostic correlation between FRGs and ccRCC has not yet been elucidated. To address this, the current study used The Cancer Genome Atlas (TCGA) dataset to explore 64 FRGs and determine their prognostic value in ccRCC. Results showed that 52 out of the 64 genes displayed significantly different expression levels in tumor tissue, and 35 out of the 52 differentially expressed genes (DEGs) were associated with overall survival. Subsequently, a four-gene prognostic signature (CD44, DPP4, NCOA4 and SLC7A11) was constructed and could successfully distinguish ccRCC patients with different prognosis in TCGA train and test sets. Furthermore, clinical ccRCC samples from our medical center were used to verify the application value of the new prognostic signature through immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Biological functional analysis implied that immune-related functions and pathways were enriched in the TCGA cohort and the immune status scores were significantly different between high- and low-risk sets. These results suggest that the four ferroptosis-related regulatory genes can act as reliable prognostic biomarkers of ccRCC, and might be exploited as potential targets of therapeutic strategies.