Protein Expression of NEK2, JMJD4, and REST in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical, Pathological, and Prognostic Findings

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 tissues of clear cell renal cell carcinoma (ccRCC) and benign nearby tissues of kidney with the aim of detecting associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates.Methods: We collected 200 samples from tumor and adjacent non-neoplastic tissues of 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 collected and analyzed.Results: NEK2 and JMJD4 expression was increased in ccRCC tissues (P=0.002 and 0.006), while REST was downregulated (P 0.001). The elevated expression of NEK2 was positively related with big 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 was positively related with big 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 was positively related to big tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates (P 0.001).Conclusion: We demonstrated that overexpression of NEK2 and JMJD4 and downregulation of REST were found in malignant than benign renal tissues and were related to unfavorable pathological findings, poor clinical parameters, and poor patient outcomes.