Interleukin 25 (IL‑25) expression in cholangiocarcinoma

Abstract

Various cytokines are involved in carcinogenesis and tumor progression. Some tumor cells produce cytokines by themselves. Using secretome analysis, a high expression of APEX-1 was found in cholangiocarcinoma (CCA) cell lines. During this secretome analysis, it was found that CCA cell lines overexpressed some cytokines and related molecules, including interleukin 25 (IL-25). In the present study, we first performed precise secretome analysis on cytokines and related molecules in CCA cell lines and identified that IL-25 was overexpressed in CCA cell lines. Then, using immunohistochemical methods, we investigated the expression of IL-25 in the cancer tissues from 20 CCA patients in Northeast Thailand. Correlation between IL-25 expression levels and patients' clinical parameters were analyzed. The results showed that IL-25 expression was significantly (P<0.0001) higher in cancerous tissues than in the normal bile ducts and in the adjacent tissues. Overexpression of IL-25 protein in CCA tissue was confirmed using western blot analysis. Moreover, IL-25 expression in cancerous tissues was significantly (P<0.0015) higher in CCA patients with metastasis than in CCA patients without metastasis. Survival analysis revealed that a high expression of IL-25 was correlated with shorter survival time of CCA patients (P=0.0260). Aberrant expression of IL-25 in CCA tissue was associated with tumor metastasis and poor prognosis, suggesting that IL-25 is a potential prognostic biomarker. Biological roles of IL-25 in CCA genesis and progression should be explored in future.

Interleukin‐25: New perspective and state‐of‐the‐art in cancer prognosis and treatment approaches

“…Although these interactions have not been verified experimentally, it is proposed that IL-25 is associated with these factors to mediate EMT in cholangiocarcinoma. 55 In HCC, it has been found that IL-25 was significantly increased in the tissue and serum of patients, and elevated IL-25 expression in the HCC tissue was negatively associated with survival rate and correlated to poor prognosis after radical hepatectomy. 45 Regarding IL-25 involvement in HCC progression, it has been proposed that this cytokine facilitates tumorigenesis via inducing M2 macrophage development through induction of ERK signaling in these cells.…”

“…Moreover, survival analysis discovered that upregulation of IL-25 was associated with shorter survival time in cholangiocarcinoma patients. 55 Further analysis regarding IL-25 involvement in cholangiocarcinoma using protein interaction software STITCH has shown that IL-25 has potential direct and indirect interaction with SMAD2, TGF-β1, NF-κB, and SNAI. It is proposed that SMAD2 and TGF-β1 expression might be involved in IL-25 elevation and EMT.…”

“…They have shown that expression of IL‐25 was significantly higher in metastatic cholangiocarcinoma compared with non‐metastatic cholangiocarcinoma patients. Moreover, survival analysis discovered that upregulation of IL‐25 was associated with shorter survival time in cholangiocarcinoma patients 55 . Further analysis regarding IL‐25 involvement in cholangiocarcinoma using protein interaction software STITCH has shown that IL‐25 has potential direct and indirect interaction with SMAD2, TGF‐β1, NF‐κB, and SNAI.…”

“…It is proposed that SMAD2 and TGF‐β1 expression might be involved in IL‐25 elevation and EMT. Although these interactions have not been verified experimentally, it is proposed that IL‐25 is associated with these factors to mediate EMT in cholangiocarcinoma 55 …”

Interleukin 25 and its biological features and function in intestinal diseases

“…Apart from promoting type 2 responses, studies have proved that IL-25 can suppress Th1 and Th17 responses in different environments including the intestine [10][11][12]. Apart from activity in inflammation and allergy reactions, IL-25 also may be involved in tumorigenesis in ways to be explored yet [13,14].…”