Can Targeting APE1 and SSRP1 Improve Survival in Muscle-Invasive Bladder Cancer?
Posted: Tuesday, May 18, 2021
Apurinic/apyrimidinic endonuclease 1 (APE1) and its interacting partner, structure-specific recognition protein 1 (SSRP1), facilitate chromatin access and DNA repair function through the histone chaperone FACT complex. This process has previously been associated with promoting drug resistance in cancer. Researchers have now found that levels of APE1 and SSRP1 tend to be abnormally high in patients with muscle-invasive bladder cancer. Further, overexpression of APE1 and SSRP1 genes appeared to be associated with poor survival.
“This suggests the usage of FACT inhibitor curaxins in muscle-invasive bladder cancer to target FACT complex and APE1 to improve chemosensitization after further validation,” stated Kishor K. Bhakat, MD, and colleagues, of the University of Nebraska Medical Center, Omaha. This retrospective study was published in the journal Heliyon.
Bladder cancer samples (n = 69) from patients who had undergone cystectomy or transurethral resection of bladder tumor were obtained from the Paraffin Tissue Bank. Tissue was stained for APE1 and SSRP1 using standard immunohistochemistry. The intensity of staining, percentage of positive cells, and histologic characteristics were recorded. Medical records from these patients provided information on overall survival. Further, the R2 Genomics Platform was utilized to generate a Kaplan-Meier curve of APEX1 and SSRP1 gene expression on overall survival from the tumor bladder urothelial carcinoma data set (n = 408).
The percentage of cells positively stained for APE1 was markedly higher in low-grade (66%) and high-grade tumors (98%), compared with normal adjacent tissues (4.2%, P < .01). Although SSRP1 was unobserved in normal tissue, there was a positive correlation between staining intensity of both APE1 and SSRP1 and tumor stage in muscle-invasive bladder cancer samples (R = .546, P < .0001). Elevation of APE1 (P < .05) and SSRP1 (P < .05) was associated with poor survival in the patients who provided tissue bank samples. Similarly, the R2 database indicated that poor survival was associated with upregulation of APEX1 (P < .05) and SSRP1 (P < .0001) in muscle-invasive bladder cancers, but not in non–muscle-invasive tumors (P > .24).
Disclosure: The study authors reported no conflicts of interest.