ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

ERK-mediated Cytoplasmic Retention of USP11 Contributes to Breast Cancer Cell Proliferation by Stabilizing Cytoplasmic p21

“…Cytoplasmic p21 was reported to act as an oncogenic protein in various cancers 19 , 22 , 56 . Since USP11 regulates cytoplasmic p21 stability, we hypothesized that USP11 may promote breast cancer cell proliferation through cytoplasmic p21.…”

Tumor suppressive role of microRNA-139-5p in bone marrow mesenchymal stem cells-derived extracellular vesicles in bladder cancer through regulation of the KIF3A/p21 axis

“…Moreover, KIF3A can inhibit the expression of p21 [ 14 ]. p21 belongs to the family of cyclin-dependent kinase inhibitors, which regulate the cell cycle by inactivating cyclin-dependent kinase, a key regulator of the cell cycle [ 15 ]. The expression of p21 is downregulated in bladder cancer, and its up-regulation is able to delay bladder cancer [ 16 , 17 ].…”

Clinicopathological and prognostic role of ROC1 in neoplasms: A PRISMA-compliant systematic review and meta-analysis

“…[6][7][8][9] In bladder cancer, esophageal squamous cell carcinoma and gastric cancer, ROC1 acts as an independent prognostic biomarker of recurrence-free survival (RFS). [6,10,11] Overall, ROC1 promotes malignant progression of cancer and elevated ROC1 expression is positively associated with poor prognosis in tumors. On the other hand, increased ROC1 expression is associated with large tumor size, lymph node metastasis (LNM) and Tumor Node Metastasis (TNM) stage in a diversity of neoplasms.…”