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A Novel Ferroptosis-Related Pathway for Regulating Immune Checkpoints in Clear Cell Renal Cell Carcinoma

Su Gao1,2, Hailong Ruan3, Jingchong Liu3

  • 1Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Frontiers in Oncology
|August 9, 2021
PubMed

Insights

Ferroptosis, a cell death form, impacts clear cell renal cell carcinoma (ccRCC). Researchers identified a ferroptosis gene signature (FeSig) for diagnosis and prognosis, revealing a link to tumor immunity and the TAZ/WNT10B pathway for potential ccRCC immunotherapy.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Ferroptosis is a distinct form of programmed cell death implicated in various diseases, particularly cancers.
  • While ferroptosis is linked to clear cell renal cell carcinoma (ccRCC) progression, its precise molecular underpinnings remain largely unknown.
  • Understanding ferroptosis's role in ccRCC is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To identify a ferroptosis-related gene signature for diagnosing and predicting outcomes in ccRCC.
  • To investigate the association between ferroptosis and tumor immunity in ccRCC.
  • To elucidate the molecular mechanisms, including potential regulatory pathways, underlying ferroptosis in ccRCC.

Main Methods:

  • Cox regression analysis was used to construct a four-gene signature (FeSig) based on ferroptosis-related genes.
  • Receiver Operating Characteristic (ROC) and survival analyses were performed to assess the diagnostic and prognostic capabilities of FeSig.
  • Weighted gene co-expression network analysis (WGCNA) was employed to identify potential regulatory mechanisms, followed by correlation and survival analyses.

Main Results:

  • The constructed four-gene signature (FeSig) demonstrated significant diagnostic and prognostic value in ccRCC.
  • Ferroptosis was found to be significantly associated with tumor immunity in the context of ccRCC.
  • The TAZ/WNT10B axis was identified as a key tumor immune-related regulatory pathway linked to ferroptosis in ccRCC.

Conclusions:

  • Ferroptosis plays a significant role in ccRCC and is closely correlated with the tumor immune microenvironment.
  • The TAZ/WNT10B signaling pathway emerges as a critical regulator in ferroptosis-associated immunity within ccRCC.
  • The TAZ/WNT10B axis presents a promising novel biomarker and therapeutic target for advancing immunotherapy in ccRCC.
Keywords:
PD-1TAZWNT10Bclear cell renal cell carcinomaferroptosisimmune checkpoints

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