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Published on: December 29, 2012
AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma
Weihao Liu1, Ying Liu2, Shisheng Chen3
1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Background:
Chromatin regulators (CRs) are capable of causing epigenetic alterations, which are significant features of cancer. However, the function of CRs in controlling Clear Cell Renal Cell Carcinoma (ccRCC) is not well understood. This research aims to discover a CRs prognostic signature in ccRCC and to elucidate the roles of CRs-related genes in tumor microenvironment (TME).
Methods:
Expression profiles and relevant clinical annotations were retrieved from the Cancer Genome Atlas (TCGA) and UCSC Xena platform for progression-free survival (PFS) data. The R package "limma" was used to identify differentially expressed CRs. A predictive model based on five CRs was developed using LASSO-Cox analysis. The model's predictive power and applicability were validated using K-M curves, ROC curves, nomograms, comparisons with other models, stratified survival analyses, and validation with the ICGC cohort. GO and GSEA analyses were performed to investigate mechanisms differentiating low and high riskScore groups. Immunogenicity was assessed using Tumor Mutational Burden (TMB), immune cell infiltrations were inferred, and immunotherapy was evaluated using immunophenogram analysis and the expression patterns of human leukocyte antigen (HLA) and checkpoint genes. Differentially expressed CRs (DECRs) between low and high riskScore groups were identified using log2|FC|> 1 and FDR < 0.05. AURKB, one of the high-risk DECRs and a component of our prognostic model, was selected for further analysis.
Results:
We constructed a 5 CRs signature, which demonstrated a strong capacity to predict survival and greater applicability in ccRCC. Elevated immunogenicity and immune infiltration in the high riskScore group were associated with poor prognosis. Immunotherapy was more effective in the high riskScore group, and certain chemotherapy medications, including cisplatin, docetaxel, bleomycin, and axitinib, had lower IC50 values. Our research shows that AURKB is critical for the immunogenicity and immune infiltration of the high riskScore group.
Conclusion:
Our study produced a reliable prognostic prediction model using only 5 CRs. We found that AURKB promotes immunogenicity and immune infiltration. This research provides crucial support for the development of prognostic biomarkers and treatment strategies for ccRCC.
Insights
This study identifies a 5-chromatin regulator (CR) signature for predicting clear cell renal cell carcinoma (ccRCC) survival. High-risk patients show increased tumor immunogenicity and better immunotherapy response, with AURKB promoting these effects.
Area of Science:
- Oncology
- Epigenetics
- Cancer Genomics
Background:
- Chromatin regulators (CRs) influence epigenetic alterations crucial in cancer development.
- The specific role of CRs in clear cell renal cell carcinoma (ccRCC) remains largely uncharacterized.
- Understanding CRs is vital for advancing ccRCC diagnostics and therapeutics.
Purpose of the Study:
- To develop a prognostic signature for ccRCC based on CRs.
- To investigate the association between CRs and the tumor microenvironment (TME).
- To identify potential therapeutic targets within CR-related genes in ccRCC.
Main Methods:
- Utilized TCGA and UCSC Xena data for ccRCC expression profiles and clinical data.
- Developed a 5-CR prognostic model using LASSO-Cox regression and validated it across cohorts.
- Assessed tumor immunogenicity, immune cell infiltration, and immunotherapy response using various bioinformatics analyses.
- Investigated the role of AURKB in ccRCC immunogenicity and TME.
Main Results:
- A robust 5-CR signature accurately predicted ccRCC patient survival.
- Higher risk scores correlated with increased tumor immunogenicity and immune cell infiltration, linked to poorer prognosis.
- The high-risk group demonstrated enhanced response to immunotherapy.
- AURKB was identified as a key driver of immunogenicity and immune infiltration in high-risk ccRCC.
Conclusions:
- A reliable 5-CR prognostic model for ccRCC was established.
- AURKB plays a significant role in promoting ccRCC immunogenicity and immune infiltration.
- This research offers valuable insights for developing novel prognostic biomarkers and targeted treatment strategies for ccRCC.
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