Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
School of Biosciences, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia.
BMC Urol. 2022 Feb 7;22(1):17. doi: 10.1186/s12894-022-00964-2.
There have been few studies regarding viral involvement in the pathogenesis of renal cell carcinoma (RCC). The aim of this study was to examine the possible association of Epstein-Barr virus (EBV) infection with clinicopathological features and cellular biomarkers including p53, p16INK4a, Ki-67 and nuclear factor-kappa B (NF-κB) in RCC tumors.
In this prospective study, 122 histologically confirmed Formalin-fixed Paraffin-embedded RCC tissue specimens along with 96 specimens of their corresponding peritumoral tissues and 23 samples of blunt renal injuries were subjected to nested polymerase chain reaction (nPCR) in order to amplify EBV DNA sequences. The expression of p53, p16INK4a, Ki-67 and NF-κB was investigated by immunohistochemistry (IHC) assay. Statistical analysis was employed to demonstrate the possible associations.
Infection with EBV was found to be significantly associated with RCC. Our results indicate that p65 NF-κB signaling pathway is probably involved in EBV-mediated RCC pathogenesis. Moreover, we found p53, Ki-67 and cytoplasmic NF-κB expression to be associated with tumor nuclear grade in RCC patients. The expression of p53 and Ki-67 was associated with primary tumor category as well. In addition, p53 overexpression was significantly more frequent among nonconventional RCC tumors than the conventional histologic type.
Infection with EBV is likely to play an important role in the development of RCC through the constitutive and permanent activation of NF-κB p65 signaling pathway. However, more experiments and supporting data are required to reach a decisive conclusion.
关于病毒在肾细胞癌（RCC）发病机制中的作用的研究甚少。本研究旨在探讨 EB 病毒（EBV）感染与 RCC 肿瘤的临床病理特征和细胞生物标志物（包括 p53、p16INK4a、Ki-67 和核因子-κB（NF-κB））之间可能的关联。
在这项前瞻性研究中，对 122 例组织学证实的福尔马林固定石蜡包埋的 RCC 组织标本以及 96 例相应的肿瘤旁组织标本和 23 例钝性肾损伤标本进行巢式聚合酶链反应（nPCR），以扩增 EBV DNA 序列。通过免疫组织化学（IHC）检测 p53、p16INK4a、Ki-67 和 NF-κB 的表达。采用统计学分析来证明可能的关联。
发现 EBV 感染与 RCC 显著相关。我们的结果表明，p65 NF-κB 信号通路可能参与 EBV 介导的 RCC 发病机制。此外，我们发现 p53、Ki-67 和细胞质 NF-κB 的表达与 RCC 患者的肿瘤核分级相关。p53 和 Ki-67 的表达与原发性肿瘤分类有关。此外，p53 过表达在非典型 RCC 肿瘤中比常规组织学类型更为频繁。
EBV 感染可能通过 NF-κB p65 信号通路的持续和永久激活在 RCC 的发生发展中发挥重要作用。然而，需要更多的实验和支持数据来得出决定性的结论。
