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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Protein Expression of NEK2, JMJD4, and REST in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical, Pathological, and
Walid S H Elsayed1, Ola A Harb1, Mohamed Ali Alabiad1
1Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Background & Objective:
Cells of renal cell carcinoma (RCC) are resistant to the most currently used chemotherapeutic agents and targeted therapies; hence, we evaluated the expression of NEK2, JMJD4, and REST in cases of clear cell renal cell carcinoma (ccRCC) and benign adjacent tissues of kidney to detect associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates.
Methods:
We collected 200 samples including tumoral and adjacent non-neoplastic tissues related to 100 ccRCC patients. All samples were evaluated for the expression of NEK2, JMJD4, and REST, and the patients were followed up for about 5 years. Tumor recurrence and survival data were documented and analyzed.
Results:
NEK2 and JMJD4 expression showed increase in ccRCC tissues (P=0.002 and 0.006), while REST was downregulated (P<0.001). The elevated expression of NEK2 was positively related ro the tumor size (P=0.015), higher grades (P=0.002), higher stages (P=0.013), distant spread (P=0.004), tumor recurrence, shorter progression-free survival (PFS) rate, and overall survival (OS) rate (P<0.001). Likewise, the high expression of JMJD4 showed positive correlation with the tumor size (P=0.047), higher grades (P=0.003), higher stages (P=0.043), distant spread (P=0.001), tumor recurrence, shorter PFS rate, and OS rate (P<0.001). Conversely, low expression of REST demonstrated positive relationship with the tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates (P<0.001).
Conclusion:
Overexpression of NEK2 and JMJD4 and downregulation of REST may be noted in malignant renal tissues compared to benign renal tissues and may be correlated with unfavorable pathological findings, poor clinical parameters, and poor patient outcomes.
Insights
NEK2 and JMJD4 are overexpressed, while REST is downregulated in clear cell renal cell carcinoma (ccRCC). These changes correlate with aggressive tumor features and poorer patient survival, indicating potential biomarkers for ccRCC progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) exhibits resistance to current therapies.
- Identifying novel molecular markers is crucial for improving ccRCC treatment strategies.
Purpose of the Study:
- To investigate the expression levels of NEK2, JMJD4, and REST in ccRCC tissues.
- To determine the association between the expression of these genes and clinicopathological features, tumor recurrence, and patient survival.
Main Methods:
- Analysis of 200 tumoral and adjacent non-neoplastic kidney tissue samples from 100 ccRCC patients.
- Evaluation of NEK2, JMJD4, and REST expression using quantitative methods.
- Long-term follow-up of patients for approximately 5 years to document recurrence and survival data.
Main Results:
- NEK2 and JMJD4 expression were significantly increased in ccRCC tissues (P=0.002 and 0.006, respectively).
- REST expression was significantly downregulated in ccRCC tissues (P<0.001).
- Elevated NEK2 and JMJD4, and decreased REST expression correlated positively with larger tumor size, higher tumor grade and stage, distant metastasis, increased tumor recurrence, and shorter progression-free survival (PFS) and overall survival (OS) rates.
Conclusions:
- Overexpression of NEK2 and JMJD4, and downregulation of REST are characteristic of malignant renal tissues compared to benign tissues.
- These molecular alterations are associated with unfavorable pathological findings and poorer patient outcomes in ccRCC.
- NEK2, JMJD4, and REST may serve as potential prognostic biomarkers for ccRCC.
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