[Differential expression of hyaluronic acid synthase family in human bladder transitional cell carcinoma and its clinical significance].

ABSTRACT

OBJECTIVE: To investigate the differential expression of the hyaluronic acid synthase (HAS) family in human bladder transitional cell carcinoma (BTCC) and its potential clinical significance. METHODS: The relative quantitative detection of the expression of HAS isoforms (HASs) was performed in 78 human BTCC tissues (mRNA & protein) and 12 normal human bladder mucosa (protein) by real-time RT-PCR and Western blot, and the results were statistically analyzed according to the clinical data. RESULTS: All the BTCC tissues expressed three HAS isoform mRNA and protein, but to a different extent, as for mRNA, HAS3 > HAS2 > HAS1 (P < 0.001), with a significant difference in HAS1/HAS2, HAS1/HAS3 and HAS2/HAS3 (P = 0.003, < 0.001, 0.006, respectively). Among the proteins, the HAS2 expression was the highest, with a significant difference in HAS1/HAS2, and HAS2/HAS3 (P = 0.004, 0.001, respectively), but not in HAS1/HAS3. The elevation of HAS1 mRNA and protein expression was significantly related with the tumor malignancy, tumor initial onset/recurrence, T1/T2 and T1/T3-4 stags, and tumor grading (P = 0.02, < 0.001, 0.038, < 0.001; 0.025, 0.031, 0.023, 0.002; respectively). The HAS2 mRNA expression was significantly related with tumor size (diameter ≤ 3.0 cm/> 3.0 cm), tumor number (single or multiple), tumor initial onset/recurrence, T-staging, and histopathological differentiation (low grade/high grade) (P = 0.012, 0.004, < 0.001, < 0.001, < 0.001, respectively), but its protein expression was not significantly different in all subgroups except with the tumor size (mass diameter > 3.0 cm/≤ 3.0 cm). However, HAS3 mRNA and protein expression had no significant difference among all the subgroups. In normal human bladder mucosa, no HAS expressions were detected. CONCLUSIONS: The abnormally high expression of the HASs further indicate the reliability of hyaluronan as a urinary marker for human BTCC. Compared with HAS1 and HAS3, HAS2 as a marker may have more usefulness in studies on human BTCC carcinogenesis or development. The high expression of HAS1 protein seems to play a more important role in the BTCC tumorigenesis, and may indicate a poor prognosis of the BTCC patients.