Expression of EZH2 in renal cell carcinoma as a novel prognostic marker

Abstract

Enhancer of zeste homolog 2 (EZH2) is a member of the Polycomb group proteins and a part of Polycomb repressive complex 2. EZH2 is important for transcriptional regulation through nucleosome modification and interaction with other transcription factors. Particularly, aberration of EZH2 has been implicated in oncogenesis and progression of various neoplasms. The objective of this study was to evaluate EZH2 expression in renal cell carcinoma (RCC), especially clear cell RCC (CRCC) and correlate the expression with prognostic factors. EZH2 expression was determined by immunohistochemical staining with additional Western blotting. High expression of EZH2 was significantly correlated with higher pT stage or more frequent distant metastases (P = 0.001 and 0.024, respectively). Survival analyses displayed that patients with high EZH2 expression had a significantly shorter disease-free survival than those with low expression (P = 0.019). High expression of EZH2 tended to reduce the overall survival, however, differences did not reach statistical significance (P = 0.066). From our results, we propose that EZH2 is a useful prognostic marker for aggressive behavior of CRCC and may be applicable as a therapeutic target molecule.Key words: enhancer of zeste homolog 2, immunohistochemistry, kidney, prognosis, renal cell carcinoma Renal cell carcinoma (RCC) originates from the renal parenchyma, and comprises 90% of primary malignant renal tumors in adults.1 Although worldwide temporal trends by kidney cancer type have not been elucidated, the incidence of RCC in the United States has continued to rise, with 58 240 new diagnoses per year and 13 040 deaths from the disease in 2010.2 RCC remains a major cause of morbidity and mortality. Approximately 40% of patients eventually die of cancer progression and RCC has the highest fatality rate of the common urologic malignancies.

Enhancer of Zeste Homolog 2 as an Independent Prognostic Marker for Cancer: A Meta-Analysis

“…Patients in the study conducted by Laitinen et al (2008) received radiotherapy rather than surgery [ 30 ]. Moreover, 16 studies enrolled patients undergoing surgery but did not provide a clear description of treatments other than surgery[ 14 , 18 , 22 – 24 , 31 – 33 , 38 , 43 , 45 , 47 , 49 , 50 , 55 , 61 ]. Thus, a sensitivity analysis was performed in which we excluded these studies, and the HR increased slightly to 2.13 (95% CI: 1.62–2.80; p <0.00001).…”

Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis

“…EZH2, as a catalytic subunit of PRC2, is one of the core components [3,6]. Emerging evidence showed that EZH2 was over-expressed in a wide range of cancers, including ovarian cancer [7], malignant gliomas [8], prostate cancer [9], cervical cancer [10] and renal cell carcinoma [11]. It affected through interacting with other molecules, target genes and signalings.…”

Down-Regulation of TSLP After EZH2 Silencing in ESCC Cell Line

“…All of these cases are concerned with beginning, progression, and metastasis of cancer. The increasing of EZH2 expression have been observed in different types of cancer such as prostate 7, breast (8), bladder (9), lung (10), liver (11), kidney (12), stomach (13), esophagus (14). In many of these cases, the expression of EZH 2 is concerned with more increasing in the number and more invasive behavior of cancerous cells, that this behavior is considered as poor prognoses.…”