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Updated: Aug 1, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Risk signature identification and NPRL2 affects sunitinib sensitivity in clear cell renal cell carcinoma
Xiaoyi Du1, Zhipeng Zhao1, Xin Zhao2
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
Tumor suppressor genes (TSGs) play a crucial role in tumorigenesis and drug resistance. We analyzed the subtypes of clear cell renal cell carcinoma (ccRCC) mediated by 8 genes contained in the 3p21.3 tumor suppressor gene cluster and their effects on TME cell infiltration based on the TCGA database. The risk score model was established by principal component analysis. The hub gene NPRL2 was selected by protein-protein interactions (PPI) analysis. The effect of NPRL2 on sunitinib sensitivity of ccRCC was verified by using CCK-8, colony formation assay, wound healing assay, transwell assay and xenograft tumor model. Changes in protein expression were detected by Western blotting. We found that 8 TSGs were all differentially expressed in ccRCC samples, which could divide ccRCC into two subtypes. The constructed risk score model could predict the prognosis and drug sensitivity of ccRCC patients, and was an independent prognostic factor for ccRCC. Over-expression of NPRL2 promoted apoptosis, inhibited EMT, decreased the phosphorylation of the PI3K/AKT/mTOR signaling pathway to inhibit its activity, and promoted the sensitivity of sunitinib to ccRCC cells. Collectively, our findings increased the understanding of TSGs in ccRCC, suggesting that NPRL2 as a TSG could enhance sunitinib sensitivity to ccRCC cells.
Insights
Tumor suppressor genes (TSGs) define clear cell renal cell carcinoma (ccRCC) subtypes and predict prognosis. NPRL2, a key TSG, enhances sunitinib sensitivity in ccRCC by inhibiting tumor growth and metastasis.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Tumor suppressor genes (TSGs) are critical in cancer development and drug resistance.
- Clear cell renal cell carcinoma (ccRCC) is a significant subtype of kidney cancer.
- The 3p21.3 gene cluster harbors important TSGs involved in tumorigenesis.
Purpose of the Study:
- To analyze ccRCC subtypes based on 8 TSGs from the 3p21.3 cluster.
- To develop a risk score model for predicting ccRCC prognosis and drug sensitivity.
- To investigate the role of the hub gene NPRL2 in ccRCC and its effect on sunitinib sensitivity.
Main Methods:
- Utilized TCGA database for gene expression analysis.
- Employed principal component analysis for risk score model construction.
- Performed protein-protein interaction analysis to identify hub genes.
- Conducted in vitro (CCK-8, colony formation, wound healing, Transwell) and in vivo (xenograft) assays to assess NPRL2 function.
- Analyzed protein expression via Western blotting.
Main Results:
- Identified 8 differentially expressed TSGs that classify ccRCC into two subtypes.
- Developed a prognostic risk score model that predicts patient outcomes and drug sensitivity.
- NPRL2 was identified as a key hub gene.
- Overexpression of NPRL2 promoted apoptosis, inhibited epithelial-mesenchymal transition (EMT), and suppressed the PI3K/AKT/mTOR pathway.
- NPRL2 overexpression enhanced sunitinib sensitivity in ccRCC cells.
Conclusions:
- The 8 TSGs and the derived risk score model offer insights into ccRCC subtypes and prognosis.
- NPRL2 acts as a tumor suppressor gene in ccRCC.
- NPRL2 enhances sunitinib sensitivity, suggesting its potential as a therapeutic target for ccRCC treatment.
