Document Type: Original Article

Authors

1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2 Modeling of Non-communicable Diseases Research Center, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran

3 Urology and Nephrology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

Background: Numerous molecular changes are involved in the development and
progression of bladder cancer. Regular follow-up of patients is crucial due to the high
recurrence rate of bladder cancer. The aim of this study is to determine the role of
B-Raf proto-oncogene, serine/threonine kinase and ZEB2 expressions in onset and
progression of bladder cancer. We have also investigated their relationships to
pathological characteristics.
Methods: We conducted this case-control study on bladder cancer and its healthy
adjacent tissue, and normal bladder tissue from patients with benign prostatic hyperplasia.
After extraction of total RNA and cDNA synthesis, quantitative expression analysis was
performed in duplicate using real-time PCR. Changes in the gene expression were
calculated according to the 2(-ΔΔCt) equation. The products were confirmed by 1% agarose
gel electrophoresis and sequenced by Bioneer Company. Data was analyzed using the
SPSS software (version 16).
Results: There was significantly greater B-Raf proto-oncogene, serine/threonine
kinase expression in 82% of bladder tumor samples compared to the adjacent tissues.
In 91.1% of tumor samples, the gene expression was also significantly higher than healthy
bladder tissues from patients with benign prostatic hyperplasia. We observed
overexpression of B-Raf proto-oncogene, serine/threonine kinase in 61.7% of the
healthy margin tissue samples compared to healthy bladder tissues of patients with benign
prostatic hyperplasia (P<0.001). Expression of ZEB2 in 52.9% of the bladder tumor
samples was significantly higher than healthy peripheral tissues. This increase was
observed in 94.1% of tumor samples compared to healthy bladder tissues of patients
with benign prostatic hyperplasia (P<0.001). Pearson correlation coefficient showed
a positive relationship between B-Raf proto-oncogene, serine/threonine kinase and ZEB2
in cancerous samples (r = 0.75) and healthy margin tissue samples (r = 0.49).
Conclusion: During the carcinogenesis process, molecular changes are seen in
healthy margin tissue. These molecular changes may be the reason for the high
recurrence rate of bladder cancer. B-Raf proto-oncogene, serine/threonine kinase can
potentially be a target cancer therapy in antisense technologies.

Keywords