Abstract
BackgroundMajority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC.Methodology and FindingsWe examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0–G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro.ConclusionsCollectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.
Highlights
Bladder transitional cell carcinoma (TCC) is one of the tumors associated with the highest morbidity and mortality among genitourinary malignancies, accounting for 90% of bladder tumors [1]
Collectively, our data in clinical specimens indicated that Sperm associated antigen 9 (SPAG9) is potential biomarker and therapeutic target for bladder TCC
SPAG9 Gene Expression in Bladder TCC Tissue Specimens SPAG9 mRNA was detected in 81% bladder TCC tissue specimens by employing RT-PCR among which 82% were of superficial non-muscle invasive and 79% were of muscle-invasive tumor specimens (Table 1)
Summary
Bladder transitional cell carcinoma (TCC) is one of the tumors associated with the highest morbidity and mortality among genitourinary malignancies, accounting for 90% of bladder tumors [1]. The standard diagnostic methods for the identification and monitoring for recurrence and progression of bladder cancer are cystoscopy [3] and urine cytology [4]. The application of these gold standard diagnostic methods is limited in the routine clinical practice due to invasive nature and cost of cystoscopy and low sensitivity of urine cytology. We analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
