T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival.
BACKGROUND
T cell immunoglobulin mucin-3 (Tim-3) was initially recognized as a pivotal immune checkpoint inhibitor that maintains immune homeostasis and tolerance. Recently, Tim-3 has been demonstrated to play an important role in tumor-associated immune suppression and aberrant Tim-3 expression has been reported in several human malignancies. However, the role of Tim-3 in bladder urothelial carcinoma (BUC) remains largely unknown. The present study aims to investigate Tim-3 expression in BUC and analyze correlations with clinicopathologic outcomes and postoperative survival.


METHODS
Tim-3 protein expressions were detected in paraffin embedded sections from 100 patients with BUC by immunohistochemistry. Expressions were correlated with clinicopathologic outcomes and postoperative survival.


RESULTS
Tim-3 protein was over-expressed in bladder cancer cells, tumor infiltrating lymphocytes and endothelial cells from patients with BUC. The expression levels of Tim-3 were significantly correlated with advanced pathological grade and T stage. Moreover, another immune checkpoint molecule programmed death receptor-1(PD-1) was also over- expressed in BUC tissues and had a significant correlation with Tim-3. Multivariate analysis showed that Tim-3 expression, as well as PD-1 expression was both independent predictors of disease-free survival and overall survival in patients with BUC.


CONCLUSIONS
Tim-3 over-expression implies adverse clinical outcomes for BUC, which suggests it is a potential prognostic biomarker and a novel therapeutic target in BUC.
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Meng
M
Yang
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Qinchao
Q
Yu
Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, China.
Jing
J
Liu
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Weiwei
W
Fu
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Yanwei
Y
Cao
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Lun
L
Yu
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Shixiu
S
Shao
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Xinsheng
X
Wang
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Haitao
H
Niu
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Yonghua
Y
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins
PD-1; Tim-3; bladder urothelial carcinoma; prognosis