Indoleamine-2,3-dioxygenase-1 expression predicts poorer survival and up-regulates ZEB2 expression in human early stage bladder cancer

Yuh-Shyan Tsai, Yeong Chin Jou, Hsin Tzu Tsai, Ian Seng Cheong, Tzong Shin Tzai

Research output: Contribution to journalArticle

Abstract

Purposes: Indoleamine-2,3-dioxygenase-1 (IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cells 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). Materials and 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. Clinicopathological correlates of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets, as well as in vitro studies. Results: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, P = 0.0005). IDO1 expression is an independent poor prognostic factor for disease progression [hazard 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 T24 cell subline demonstrated that IDO1 expression can up-regulate ZEB2 expression probably through miR-200c signaling. Conclusion: IDO1 expression predicts poorer survival and up-regulates ZEB2 expression in human bladder cancer.

Original languageEnglish
JournalUrologic Oncology: Seminars and Original Investigations
DOIs
Publication statusPublished - 2019 Jan 1

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Urinary Bladder Neoplasms
Up-Regulation
Survival
Carcinoma
Tryptophan
Urinary Bladder
Vimentin
Urinary Tract
Fibronectins
Paraffin
Disease Progression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Cite this

@article{8f86df6a8f5e4f318702a966e6c6f84f,
title = "Indoleamine-2,3-dioxygenase-1 expression predicts poorer survival and up-regulates ZEB2 expression in human early stage bladder cancer",
abstract = "Purposes: Indoleamine-2,3-dioxygenase-1 (IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cells 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). Materials and 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. Clinicopathological correlates of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets, as well as in vitro studies. Results: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, P = 0.0005). IDO1 expression is an independent poor prognostic factor for disease progression [hazard 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 T24 cell subline demonstrated that IDO1 expression can up-regulate ZEB2 expression probably through miR-200c signaling. Conclusion: IDO1 expression predicts poorer survival and up-regulates ZEB2 expression in human bladder cancer.",
author = "Yuh-Shyan Tsai and Jou, {Yeong Chin} and Tsai, {Hsin Tzu} and Cheong, {Ian Seng} and Tzai, {Tzong Shin}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.urolonc.2019.05.005",
language = "English",
journal = "Urologic Oncology",
issn = "1078-1439",
publisher = "Elsevier Inc.",

}

Indoleamine-2,3-dioxygenase-1 expression predicts poorer survival and up-regulates ZEB2 expression in human early stage bladder cancer. / Tsai, Yuh-Shyan; Jou, Yeong Chin; Tsai, Hsin Tzu; Cheong, Ian Seng; Tzai, Tzong Shin.

In: Urologic Oncology: Seminars and Original Investigations, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Indoleamine-2,3-dioxygenase-1 expression predicts poorer survival and up-regulates ZEB2 expression in human early stage bladder cancer

AU - Tsai, Yuh-Shyan

AU - Jou, Yeong Chin

AU - Tsai, Hsin Tzu

AU - Cheong, Ian Seng

AU - Tzai, Tzong Shin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purposes: Indoleamine-2,3-dioxygenase-1 (IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cells 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). Materials and 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. Clinicopathological correlates of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets, as well as in vitro studies. Results: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, P = 0.0005). IDO1 expression is an independent poor prognostic factor for disease progression [hazard 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 T24 cell subline demonstrated that IDO1 expression can up-regulate ZEB2 expression probably through miR-200c signaling. Conclusion: IDO1 expression predicts poorer survival and up-regulates ZEB2 expression in human bladder cancer.

AB - Purposes: Indoleamine-2,3-dioxygenase-1 (IDO1) is a key enzyme of tryptophan metabolism which regulates T cell function in immune cells 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). Materials and 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. Clinicopathological correlates of IDO1 expression and the prognostic values in human bladder cancer were explored. External validation was performed with 4 published bladder cancer datasets, as well as in vitro studies. Results: As compared with normal adjacent tissues, UC exhibited a higher frequency of IDO1 expression (chi-square, P = 0.0005). IDO1 expression is an independent poor prognostic factor for disease progression [hazard 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 T24 cell subline demonstrated that IDO1 expression can up-regulate ZEB2 expression probably through miR-200c signaling. Conclusion: IDO1 expression predicts poorer survival and up-regulates ZEB2 expression in human bladder cancer.

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