JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Developing and experimentally validating a glucocorticoid signaling-related gene signature to evaluate the prognosis and immunotherapeutic response in kidney renal clear cell carcinoma

  • 0Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Plos One +

|

October 13, 2025

|

October 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

A new gene signature involving ACADM, ANGPTL4, and NFKB2 predicts prognosis and immunotherapy response in kidney renal clear cell carcinoma (KIRC). This finding offers insights for personalized KIRC treatment strategies.

Area Of Science

  • Oncology
  • Molecular Biology
  • Immunology

Background

  • Glucocorticoids influence cancer development and progression.
  • The prognostic role of glucocorticoid signaling genes in kidney renal clear cell carcinoma (KIRC) is not well understood.
  • KIRC patients show higher serum glucocorticoid levels than healthy individuals.

Purpose Of The Study

  • To identify and validate a gene signature related to glucocorticoid signaling for predicting prognosis and immunotherapy response in KIRC.
  • To investigate the association of this gene signature with immune cell infiltration and T cell exhaustion in KIRC.

Main Methods

  • Curated glucocorticoid signaling genes from MSigDB.
  • Utilized TCGA-KIRC cohort for training and 7 independent KIRC cohorts for validation.
  • Employed LASSO, random forest, and multivariate Cox regression analyses to develop the gene signature.
  • Performed meta-analyses, spatial transcriptomics, and in vivo experiments.

Main Results

  • Identified a three-gene signature (ACADM, ANGPTL4, NFKB2) as a robust prognostic indicator in KIRC across multiple cohorts.
  • Observed increased NFKB2+ cell infiltration and decreased ACADM+/ANGPTL4+ cell levels in KIRC tissues.
  • Found a positive correlation between the signature and CD8+ T cell infiltration, T cell exhaustion, and predicted immunotherapy response.
  • NFKB2 knockdown inhibited tumor growth and CD8+ T cell expansion in vivo, an effect reversed by corticosterone.

Conclusions

  • Developed and validated a glucocorticoid signaling-related gene signature for predicting KIRC prognosis and immunotherapy response.
  • The signature serves as a valuable tool for guiding personalized treatment strategies in KIRC.
  • Highlights the intricate role of glucocorticoid signaling in KIRC tumorigenesis and immune evasion.