ABSTRACT
Bladder cancer (BC) is one among the most common and lethal urothelial malignancies worldwide. The expression of cancer-testis (CT) antigens in some tumours and restricted expression among normal tissues make CT antigens as attractive vaccine targets. In this context, we evaluated Centrosomal protein 55 kDa (CEP55), which is specifically expressed in normal human testis and various malignancies. Until the expression pattern of CEP55 in transitional cell carcinoma (TCC) of human urinary bladder and its clinical significance are not known. The aim of the present study is to evaluate mRNA/protein expression of CEP55 in TCCs of urinary bladder and correlate its expression with the clinicopathological characteristics of BC patients. In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to investigate mRNA/protein expression of CEP55 in TCC. Independent Student's t test, ANOVA and Chi-square (χ(2)) were used to analyze the data statistically. We observed CEP55 mRNA overexpression in testis and 48.7% of BC patients. Relative mean fold expression of CEP55 mRNA was found to be significantly (p<0.01) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (7.88±3.88 vs. 4.75±2.30, p=0.01). CEP55 protein expression was evaluated using IHC and cytoplasmic staining pattern was recorded in formalin fixed, paraffin-embedded (FFPE) bladder tumour tissues. No significant difference was observed in protein expression of CEP55 between the two groups (NMIBC and MIBC patients) (72.2% vs. 69.0%, p=0.774). No significant protein expression of CEP55 was observed among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Our study results suggest that CEP55 mRNA/protein expression was observed is specific to TCC of human urinary bladder and might be used as a diagnostic biomarker and vaccine target in development of BC specific immunotherapy.
Subject(s)
Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Cell Cycle Proteins/genetics , Gene Expression , Nuclear Proteins/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Adult , Aged , Cell Cycle Proteins/metabolism , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Nuclear Proteins/metabolism , RNA, Messenger/genetics , Risk FactorsABSTRACT
The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC). We detected PBK/TOPK mRNA overexpression in BC and human normal testis tissues using RT-PCR. Using qRT-PCR revealed a higher expression of PBK/TOPK in BC tissues than their adjacent noncancerous tissues (ANCTs) (p<0.0001). Cytoplasmic expression of PBK/TOPK protein was found to be positive in 64.6% (42 of 65) BC patients. Expression of PBK/TOPK protein was found to be significantly higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC) (86.1% vs. 37.9%, p<0.001). The immunohistochemical (IHC) expression of PBK/TOPK was found to be significantly (p<0.001) associated with the stage of disease. Study findings suggest that the PBK/TOPK mRNA/protein expression is specific to human BC and might be used as a novel target for development of cancer immunotherapy and diagnostic biomarker.
Subject(s)
Carcinoma, Transitional Cell/genetics , Mitogen-Activated Protein Kinase Kinases/biosynthesis , Mitogen-Activated Protein Kinase Kinases/genetics , Urinary Bladder Neoplasms/genetics , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Carcinoma, Transitional Cell/pathology , Female , Humans , Male , Middle Aged , RNA, Messenger/biosynthesis , Testis/metabolism , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Cell regulatory G2/M phase proteins are the key regulators of mitosis and have been reported with abnormal expressions in various malignancies. AIM: To determine the expressions of these proteins in neoplastic uterine cervix tissue. MATERIALS AND METHODS: This study evaluates the G2/M phase regulatory protein expression of Cyclin B1, Aurora-B, Pololike kinase 1 (PLK1) and LIM kinase1 (LIMK1) in tissues of 25 normal (control), 16 dysplastic (dysplasia) and 34 neoplastic (cancer) patients of uterine cervix. The expressions of different proteins were obtained by using Western Blot technique. STATISTICAL ANALYSIS: One way analysis of variance (ANOVA), Pearson correlation, Kaplan-Meier and other tests are used for analysis. RESULTS AND CONCLUSION: The level of expression of LIMK1 in cervical cancer patients was found to be significantly higher (P < 0.01) than both the controls and dysplasia. The expression of Aurora B and PLK1 in cervical cancer patients was also found to be significantly higher ( P < 0.05) than controls but it did not differ with dysplasia. However, the expression of Cyclin B1 was similar among cervical cancer patients, dysplasia and controls ( P> 0.05). The expression of all the above proteins showed significant ( P < 0.01) and inverse relation with the survival of cancer patients. Among the selected candidate proteins, it was LIMK1 that showed the most positive correlation with the aggressiveness of the disease and negative correlation (r= -0.64; P < 0.01) with the survival of patients.
