Elnaz Zahiri - Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
HamidReza Ghorbani - Kidney Transplantation Complications Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Ali Moradi - Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran & Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Hassan Mehrad-Majd - Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Fariba Mohammadi - Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Noorieh Sharifi Sistani - Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Seyed Isaac Hashemy - Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-۱ receptor (NK-۱R) system in cancers. The potential prognostic role and the interaction of SP and NK-۱R in bladder tumor are yet to be elucidated. Methods: Serum samples from ۲۲ primarily diagnosed patients with bladder cancer as well as ۲۲ healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-۱R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry. esults: Serum SP levels in patients with bladder cancer were higher than the healthy group (p< ۰.۰۰۱) and had a significant correlation with NK-۱R staining intensity (p< ۰.۰۰۱), percentage of stained cells (p< ۰.۰۰۱), and NK-۱R tissue distribution. Also, the immunoreactivity of NK-۱R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-۱R levels with clinical characteristics including tumor size (p= ۰.۳۳), tumor stage (p= ۰.۲۹), grade (p= ۰.۹۳), NK-۱R staining intensity (p= ۰.۵۳), and percentage of stained cells (p= ۰.۳۲). Conclusions: According to our findings, despite the lack of association between SP and NK-۱R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-۱R in bladder cancer.

Keywords: Biomarker, Bladder cancer, Neurokinin-۱ receptor, Substance P, Prognosis.