Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia Governorate, 35211, Egypt.
General hospital, Shebin El-Kom, Menoufia Governorate, Egypt.
Diagn Pathol. 2020 Apr 7;15(1):33. doi: 10.1186/s13000-020-00947-7.
Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin- Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients.
Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer.
Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients.
High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.
膀胱癌（BC）是埃及最常见的恶性肿瘤之一，约占男女癌症的 8.7%，男性更为常见，因此有必要确定有价值的预测和预后标志物。Cullin-RING 连接酶（CRL）在细胞周期相关蛋白或其他蛋白（如 DNA 复制蛋白、信号转导蛋白）的泛素化中发挥重要作用。Cullin-1 调节因子（ROC-1）是 CRL 的关键亚基。P21 属于细胞周期蛋白依赖性激酶抑制剂（CKI）家族，通过使细胞周期关键调节因子细胞周期蛋白依赖性激酶失活来调节细胞周期。CAIX 是碳酸酐酶家族的一个高度活跃的成员，作为缺氧标志物引起了广泛关注。缺氧是包括膀胱癌在内的许多肿瘤快速生长的结果，是基因表达和对化疗和放疗的耐药性的重要调节因子。因此，本研究旨在评估 ROC-1、CAIX 和 P21 的作用及其与埃及患者膀胱癌临床病理特征的关系。
使用标准免疫组织化学技术，评估 80 例原发性膀胱癌和 15 例正常膀胱标本作为对照组的 ROC-1、CAIX 和 P21 表达。膀胱癌病例包括 50 例肌层浸润性膀胱癌和 30 例非肌层浸润性膀胱癌。
ROC-1、CAIX 和 P21 在膀胱癌中的过度表达与固有肌层浸润和高级别膀胱癌显著相关。ROC-1、CAIX 和 P21 在原发性膀胱癌病例中呈显著负相关。CAIX 在膀胱癌中的表达明显高于对照组。关于生存分析，ROC-1、CAIX 和 P21 的表达并不影响膀胱癌患者的生存。
ROC-1、CAIX 和 P21 的高表达可能是识别膀胱癌预后不良因素的有前途的潜在生物标志物，可作为癌症治疗的潜在靶点。
