Presentation Authors: Ian Seng Cheong*, Chia-Yi, Taiwan, Yuh-Shyan Tsai, Tainan, Taiwan, Yeong-Chin Jou, Chia-Yi, Taiwan, Hsin-Tzu Tsai, Tzong-Shin Tzai, Tainan, Taiwan
Introduction: Indoleamine-2,3-dioxygenase -1(IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cell and little is known about the role of IDO1 expression in bladder cancer cells. The study is aimed to evaluate the clinical relevance of IDO1 expression in human bladder urothelial carcinoma (UC).
Methods: One hundred and sixty paraffin-embedded UC tissues (130 bladder, 30 upper urinary tract) and 47 adjacent normal tissues were retrieved for IDO1 immunostaining. Urine samples from UC and non-UC patients were collected before surgery for measuring the concentration of tryptophan and its metabolites. Clinico-pathological correlate of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets. The association between IDO1 and epithelial-mesenchymal-transition markers were explored from these 4 datasets and further in vitro cell studies were performed.
Results: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, p=0.0005). There were a significantly lower urine tryptophan concentration and higher 3-hydroxyanthranilic acid/tryptophan ratio in UC patients than in the non-UC patients (both p values, < 0.05). IDO1 expression is an independent poor prognostic factor for disease progression [harzard ratio and 95% confidence interval, 3.80 (1.46-9.86), p=0.006]), which is associated with decreased number of intratumoral infiltrating CD8+ lymphocyte (unpaired t-test, p=0.026). External validation showed that patients with higher IDO1 expression exhibit decreased disease-specific survival than those with lower IDO1 expression. Furthermore, IDO1 expression correlated positively with the expression of several EMT markers, including ZEB2, fibronectin and vimentin. The in vitro cell studies using T24 sublines demonstrated that IDO1 expression can upregulate ZEB2 expression through miR-200c signaling.
Conclusions: IDO1 expression is an independent poor factor for patients' survival which may enhance ZEB2 expression through miR200c signaling.