Indoleamine 2,3-dioxygenase 1 expression predicts cholangiocarcinoma patient survival

Cholangiocarcinoma (CCA) is a prevalent hepatobiliary disease in northeast Thailand, where late diagnosis and limited treatment options contribute to poor prognosis. The kynurenine pathway (KP) of tryptophan metabolism, is controlled by two key enzymes indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2) linking with downstream effector aryl-hydrocarbon receptor (AhR) signaling, which has been tied to immune escape and tumor growth but its clinical relevance in CCA remains unclear.

Formalin-fixed paraffin-embedded tissues from 91 CCA patients were analyzed by immunohistochemistry on tissue microarrays to assess IDO1, TDO2, and AhR expression. Staining was scored by the Allred system and classified into low and high groups based on optimum cut-off points. Associations with clinicopathological features, preoperative laboratory findings, and overall survival were examined using chi-square tests, Kaplan-Meier analysis, and Cox regression.

All proteins were differentially expressed in tumor and immune cells. In survival analysis, advanced tumor stage (p = 0.031), lack of chemotherapy (p < 0.001), early recurrence (p < 0.001), and high IDO1 expression (p = 0.007) predicted poor outcomes. Multivariate analysis confirmed chemotherapy (HR = 3.97, p < 0.001), recurrence (R = 10.98, p < 0.001), and high IDO1 (HR = 2.06, p = 0.008) as independent prognostic factors. For other clinicopathological features, we found that IDO1 expression was significantly associated with elevated serum CEA (p = 0.003), increased total protein (p = 0.001), and higher tumor-infiltrating lymphocytes (p = 0.033). TDO2 correlated with moderate-poor differentiation (p = 0.031) and serum ALP (p = 0.019), while AhR expression was linked to serum albumin (p = 0.004).

This finding indicates that high IDO1 expression is an independent prognostic factor linked to poorer patient outcomes, suggesting its potential as a biomarker for prognosis and treatment planning in CCA.