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

Abstract

To investigate the differential expression of the hyaluronic acid synthase (HAS) family in human bladder transitional cell carcinoma (BTCC) and its potential clinical significance. 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. 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. 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.