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Low EGR1 expression predicts poor prognosis in clear cell renal cell carcinoma
Zheng-Yan Zhang1, Shi-Long Zhang1, Hui-Ling Chen1
1Key Laboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer (SMHC), and Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai 201100, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201100, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is resistant to conventional therapy due to the deletion of the von Hippel-Lindau (VHL) gene, and novel treatment options are urgently needed. Here, using tissue microarray analysis of 445 cancer tissues and 326 adjacent normal renal tissues obtained from patients with ccRCC, we present the early growth response-1 (EGR1) protein levels are significantly decreased in ccRCC cancer tissues. Consistently, the EGR1 mRNA expression also decreased in cancer tissues based on the transcriptomic data for 599 tumor and normal samples from The Cancer Genome Atlas. Moreover, Patients with ccRCC presenting low EGR1 expression are more prone to exhibit metastasis and a poor prognosis than those with high EGR1 expression. By multivariate Cox regression analysis, EGR1 is determined to serve as an independent prognostic factor for patients with ccRCC. Further cellular biochemical function analyses show that EGR1 may inhibit proliferation, invasion and metastasis of ccRCC. These findings will deepen our understanding of EGR1 function and shed light on precise treatment for ccRCC patients.
Insights
Early growth response-1 (EGR1) protein is decreased in clear cell renal cell carcinoma (ccRCC), indicating it may be a target for new therapies. Lower EGR1 levels correlate with increased metastasis and poorer prognosis in ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) presents resistance to conventional treatments, often linked to von Hippel-Lindau (VHL) gene deletion.
- Novel therapeutic strategies for ccRCC are critically needed due to treatment resistance.
Purpose of the Study:
- To investigate the role of early growth response-1 (EGR1) in ccRCC.
- To determine if EGR1 expression levels correlate with patient prognosis and disease characteristics.
Main Methods:
- Tissue microarray analysis of 445 ccRCC tissues and 326 adjacent normal renal tissues.
- Analysis of transcriptomic data from The Cancer Genome Atlas (TCGA) for 599 tumor and normal samples.
- Multivariate Cox regression analysis and cellular biochemical function assays.
Main Results:
- Early growth response-1 (EGR1) protein and mRNA levels are significantly decreased in ccRCC tissues compared to normal tissues.
- Low EGR1 expression in ccRCC patients is associated with increased metastasis and a poorer prognosis.
- EGR1 serves as an independent prognostic factor for ccRCC patients.
Conclusions:
- EGR1 downregulation is a key feature of ccRCC and is linked to adverse outcomes.
- EGR1 may function as a tumor suppressor by inhibiting ccRCC proliferation, invasion, and metastasis.
- These findings highlight EGR1 as a potential therapeutic target for precise ccRCC treatment.
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