Expression and prognostic value of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma

Abstract

Objective To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral resection of bladder tumor. Methods A retrospective analysis was made of 194 specimens who underwent transurethral resection of bladder tumors in our hospital from January 2014 to January 2016 and completed follow-up. The expression intensity of CA-IX and the clinical data of the patients were analyzed, and the subjects were divided into positive group and negative group according to the expression intensity of CA-IX. The age, gender, T stage, degree of differentiation, tumor number, tumor diameter, recurrence of each group was analyzed. Logistic univariate and multivariate analysis was used successively to find independent influencing factors for predicting the recurrence of bladder urothelial carcinoma after resection. The Kaplan–Meier survival curve was drawn according to the relationship between CA-IX expression intensity and postoperative recurrence. Results The positive expression rates of CA-IX in bladder urothelial carcinomas were 68.1% (132/194). The positive expression of CA-IX had no statistical significance with age, gender and tumor diameter (P > 0.05), while the positive expression of CA-IX had statistical significance with tumor T stage, tumor differentiation, tumor number and recurrence (P < 0.05); Logistic regression analysis showed that clinical T stage, tumor differentiation, tumor number, and CA-IX expression intensities were independent risk factors for predicting recurrence of bladder urothelial carcinoma after resection (P < 0.05); There were 59 cases of recurrence in the positive expression of CA-IX group, with a recurrence rate of 44.69% (59/132), and 17 cases of recurrence in the negative expression group, with a recurrence rate of 27.41% (17/62). The mean recurrence time of CA-IX positive group was 29.93 ± 9.86 (months), and the mean recurrence time of CA-IX negative group was 34.02 ± 12.44 (months). The Kaplan–Meier survival curve showed that the recurrence rate and recurrence time of patients with positive expression of CA-IX in bladder urothelial carcinomas were significantly higher than those of patients with negative expression of CA-IX. Conclusion CA-IX is highly expressed in bladder urothelial carcinoma, is a good tumor marker, and can be used as a good indicator for predicting the recurrence of bladder urothelial carcinoma after transurethral resection of bladder tumor.

Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer

“…These pH regulators, such as CAIX, may also play a role in the cells’ sensitivity to AZD3965. CAIX is overexpressed in UBC and has been associated with high recurrence rates [ 60 , 61 ]; it seems to facilitate monocarboxylate transportation by binding to CD147, thus enhancing MCT1/4 activity [ 62 ]. Thus, although AZD3965 may decrease lactate exportation through MCT1 targeting, this may not result in a significant decrease in intracellular pH due to CAIX interference in the pH balance.…”

Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect

“…Bladder cancer, similarly to other malignancies, exhibits this glycolytic phenotype (reviewed in [16][17][18]). Several studies reported significant associations between aggressive tumor features and poor prognosis, and the upregulation of glucose transporters [19], glycolytic enzymes and their downstream players [20][21][22][23][24], pH regulators [25], and lactate transporters [26,27]. Genetic and/or pharmacological inhibition of these molecules suppressed aerobic glycolysis, cell proliferation, migration and invasion in vitro and tumor growth in vivo [20,23,24,[28][29][30][31][32].…”