| BackgroundWorldwide,the malignant tumor is the first etiological factor of human.In C hina,bladder cancer is considered as the most common malignancy in urology departments.In recent one decade,the incidence rate of bladder cancer has been inclined on the increasing tendency year by year,no matter in males or females,respectively,in urban or rural.Besides that,bladder urothelial carcinoma is the most frequent ly pathological and histological type of bladder cancer,accounting for 90%.Though the technology of surgical therapy,perfusion chemotherapy and neo-adjuvant radio-chemotherapy for bladder urothelial cancer have achieved great progresses,occult recurrence and metastasis of bladder urothelial carcinoma are still serious threats to the survival of patients,reducing the patients' qualities of life.As the gradually deepening understanding of the molecular mechanism in bladder urothelial carcinoma,investigators aim to explore and seek the tumor biomarkers which could accurately predict and evaluate the prognosis of these patients.An ocean of recent studies suggested that the Zn-alpha2-glycoprotein(AZGP1)involved in a wide variety of metabolic pathways and processes of tumor occurrence and differentiation.It was expressed as a carcinoma correlated protein significantly and differently in the prostate,pancreas and breast cancer,being considered as a potential tumor biomarker.However,a few of studies illustrated the expression level of AZGP1 in bladder urothelial carcinoma.Therefore,it is highly significant that we should research the expression level of AZGP1 and analyze its correlation with clinical prognosis in bladder urothelial cancer.Objectives1.To compare the differences of AZGP1 expression levels between bladder urothelial cancer tissues and matched adjacent non-cancerous tissues.2.To illustrate the expression level of AZGP1 in various pathological grades and clinical stages of bladder urothelial cancer tissues and analyze the correlations between clinical and pathological parameters with its expression levels.3.To explore the significance of AZGP1 expression for predicting clinical prognosis of patients suffering bladder urothelial carcinoma.Methods1.The clinic samplesWe collected tissue samples,accounting for 184,including 10 of matched adjacent non-cancerous tissues and 174 of carcinoma tissues,from total 174 patients offered transurethral cystoscop ic biopsy and cystectomy with bladder urothelial carcinoma who were treated at the Department of Urology,the Second Affiliated Hospital of Nanchang University during 2011 and 2014.The patients were never given preoperational radiotherapy and chemotherapy and the samples were totally confirmed by pathology.2.We detected the m RNA expression levels of AZGP1 in 10 paired tissues of both bladder urothelial carcinoma and the matched adjacent non-cancerous ones by the biological molecular technique of real-time quantitative polymerase chain reaction(qRT-PCR).In addition,t test or rank-sum test of paired sample was utilized to compare the differences of AZGP1 expression levels.3.We confirmed the pathological diagnosis of all above enrolled samples by hematoxylin-eosin staining.4.We examined the expression levels of AZGP1 in various pathological grades and clinical stages of 174 cases of bladder urothelial cancer tissues by immunohistochemistry and used C hi-square test or Fisher's exact probability method to analyze the relationship between clinical and pathological parameters with its expression levels.What's more,Kaplan-Meier survival analysis and Log-rank test were performed to compare and assess the curves of the relevance of AZGP1 expression and the survivals,including overall and recurrence-free ones.Meanwhile,multivariate Cox proportional regression model was taken to analyze the correlation between the clinical and pathological feature parameters and expression of AZGP1 in 174 cases of bladder urothelial carcinoma.Finally,we tried to discuss the influence factors of prognosis from the AZGP1 expression.Results1.The AZGP1 expression level was exactly lower in the tumor-bearing tissues,compared with the matched adjacent non-cancerous bladder tissues(P<0.05).2.We found that high-grade urothelial carcinoma samples were low expression of AZGP1 in 44 cases of 70(62.82%)and the low-grade urothelial carcinoma samples were high expression of AZGP1 only in 59 cases of 104(53.8%);Moreover,high expression of AZGP1 of NMIBC was in 76 cases of 144(52.78%)and low expression of AZGP1 of MIBC was in 30 cases of 21(70.00%).3.Our data showed that the levels of AZGP1 expression in 174 cases were strongly correlated with tumor cell differentiation(P=0.013)and tumor style(P=0.028)of patients with bladder urothelial cancer.What's more,if the differentiation degree of ladder urothelial cancer cell is high,the expression level of the AZGP1 is correspondingly high;respectively,if the cells invade deeply to the muscular layer or ex-muscular tissue,the expression of AZGP1 level is correspondingly low.4.Our statistical analysis revealed that the expression of AZGP1 was closely correlated with OS(P=0.019)of bladder urothelial cancer,and RFS(P=0.006).Moreover,multivariate Cox regression analyses showed that expression of AZGP1 was an independent prognostic factor in patients with bladder urothelial cancer,respectively,OS(P=0.046,hazard ratio=3.214,confidence interval 1.008 to9.341)and RFS(P=0.005,hazard ratio=4.507,confidence interval 1.730 to 12.412).Conclusions1.Compared with normal bladder tissues,AZGP1 expression in bladder urothelial carcinoma is in a low level.2.AZGP1 expression was associated with the degree of differentiation and invasion in bladder urothelial carcinoma.3.AZGP1 probably acts as a suppressor in bladder urothelial cancer.4.As an independent and potential tumor biomarker,AZGP1 may evaluate and predict the clinical prognosis of bladder urothelial carcinoma patients. |
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