膀胱癌病人之尿液蛋白的初步研究

黎赫、吳勝堂、曹智惟、蒙恩、查岱龍、孫光煥、于大雄、張聖原、周孟翰

國防醫學院三軍總醫院外科部泌尿外科

Preliminary investigation of urinary protein profiles in bladder cancer patients

Ho Li, Shen-Tang Wu, Chih-Wei Tsao, En Meng, Tai-Lung Cha, Guang-Huan Sun, Dah-Shyong Yu, Sun-Yran Chang, Meng-Han Chou

Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Purpose: We hypothesize that the urinary immune checkpoint protein panel may vary between different stages of bladder cancer patients and healthy subjects. Our aim is to analyze this panel in bladder tumors predominantly undergoing various intravesical therapies, and to compare its presence in cases of bladder tumor recurrence with that in healthy subjects.

Materials and Methods: Thirty patients with bladder cancer referred from the Urology Division of TSGH, along with twenty healthy controls aged 20 years and above, were enrolled. Urine samples were collected and analyzed. Demographic data and concurrent blood biochemistries were recorded. Urine samples were processed and stored before analysis using ProcartaPlex® Multiplex Immunoassays for quantitative measurement of immune checkpoint proteins (IDO, PD-1, PD-L1, PD-L2, TIM-3, CD27, CD28, CD80, CD135, CD137). Statistical analysis was conducted using Dunn's multiple comparison test (P<0.05). This study was approved by the Joint Institutional Review Board of the Tri-Service General Hospital (TSGH IRB no. 2-106-05-077).

Results: Significant differences in the quantitative measurement of immune checkpoint proteins, including CD137, CD28, and TIM-3 (P<0.01), IDO, PD-L1 (P<0.05), and CD27 (P=0.000), were observed. PD-L2 expression was higher than in the control group, necessitating further investigation into potential influencing factors such as medication, treatment strategy and disease status. Urinary proteomic studies revealed significant associations between IDO, PD-L1, TIM-3, CD28, CD80, CD137, CD27, CD152, and bladder cancer prognosis. Correlation analysis showed a negative correlation between CD28 and CD137 (P=0.045). Our preliminary study is still limited by a small sample size and high heterogeneity among subjects. Further research is needed to confirm its effectiveness.

Conclusions: Urine is exceptionally promising body fluid for biomarker research due to its noninvasive collection and proximity to bladder tumors. PD-L2, similar to PD-L1, may play a role in regulating T cell immune response and immune tolerance, though its exact function remains controversial. For the optimal uses of immune checkpoint inhibitors, the prognostic role of biomarkers in bladder cancer treatment, including the potential use of urine protein profiles, requires further investigation.