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Abstract
Purpose
The HedgehogGli (HHGli) signaling pathway controls many aspects of tissue patterning, cell proliferation, differentiation and regeneration, and regulates the number of cells in various organs. Inappropriate and uncontrolled activation of the HHGli signaling pathway has been demonstrated in a variety of human cancers. The Gli1, Gli2, and Gli3 genes encoding the Gli family transcription factors play a role as HH effectors. This study examined the significance in Gli2 and Gli3 expression in human bladder cancer.
Materials and Methods
The tumor tissues were obtained from 144 patients with a primary bladder cancer. The mRNA levels of Gli2, and Gli3 were examined using a real-time polymerase chain reaction (PCR) assay in 144 tumor specimens, and immunohistochemical staining was performed on 127 tumor paraffin blocks. The relationships between their expression and the pathological or clinical characteristics, such as tumor stage, grade, recurrence and progression were also analyzed.
Results
Gli2 mRNA expression was higher in the invasive bladder tumors than in the superficial bladder tumors (p＜0.001) but, there was no difference in Gli3 mRNA expression according to the tumor stage and grade. The multivariate Cox regression model revealed that Gli2 mRNA expression (hazards ratio (HR): 2.329, 95% confidence interval (CI): 1.043-5.202, p=0.039) was the only strong predictor of superficial bladder tumor recurrence. Kaplan-Meier analysis also showed identical results (log-rank test, p=0.043).
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Fig. 2.
Immunohistochemical staining of Gli2 in the normal bladder mucosa (A), superficial bladder tumor (B), invasive bladder tumor (C) and Gli3 in normal bladder mucosa (D), superficial bladder tumor (E), invasive bladder tumor (F).
Table 1.
Clinical and pathological features of the primary bladde transitional cell carcinomas
Table 2.
Gli2 and Gli3 mRNA expression levels of primary bladder transitional cell carcinomas
| Variables | Gli2* | p-value† | Gli3* | p-value† |
|---|---|---|---|---|
| Stage | ＜0.001 | 0.649 | ||
| Superficial | 3.8 (2.9-4.9) | 6.3 (4.9-8.2) | ||
| Invasive | 13.9 (9.3-20.7) | 7.0 (4.6-10.8) | ||
| Grade | 0.155 | 0.617 | ||
| Low | 5.3 (3.9-7.1) | 6.9 (5.3-8.9) | ||
| High | 7.6 (5.0-11.5) | 6.1 (4.0-9.3) |
Table 3.
Multivariate analysis for the prediction the recurrence of superficial bladder cancer
Table 4.
Gli2 and Gli3 immunohistochemical staining scores in primary bladder transitional cell carcinomas
| Variables | No. (%) | Gli2 | p-value* | Gli3 | p-value* |
|---|---|---|---|---|---|
| Stage | 0.008 | 0.039 | |||
| Superficial | 76 (59.8) | 5.47±2.16 | 6.03±2.15 | ||
| Invasive | 51 (40.2) | 6.21±2.27 | 6.97±2.67 | ||
| Grade | 0.023 | 0.010 | |||
| Low | 80 (63.0) | 5.34±1.77 | 5.96±2.37 | ||
| High | 47 (37.6) | 6.28±2.62 | 7.11±2.51 |
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