The aberrant expression of CD39 is associated with the dismal outcome of patients with cholangiocarcinoma

• DOI: 10.1007/s44272-025-00028-0
• Publication Date: 2025-02-25T07:41:43Z
• Authors: Bohao Zheng; Sheng Shen; Jiwen Wang; Wentao Sun; Wenze Wan; Jiaying Liu; Dexiang Zhang; Xiaoling Ni; Tao Suo; Han Liu; Xiaojian Ni; Houbao Liu

Abstract

Purpose To investigate the biological function and the underlying mechanism of CD39 in cholangiocarcinoma.

Methods Quantitative reverse transcription PCR (RT-qPCR), western blot (WB), and immunohistochemistry staining was used to evaluate the expression level of CD39 in cholangiocarcinoma. Kaplan–Meier and Cox hazard ratio regression analyses were implicated to evaluate the prognostic significance of CD39. Cell counting kit-8 (CCK-8) was carried out to evaluate the proliferative capacity, while transwell assay was used to detect the migration and invasion ability. In addition, B-NDG mice were used for the in vivo assay. The potential protein binding with the CD39 was identified through co-immunoprecipitation.

Results CD39 was aberrantly expressed in the tumor tissue and cholangiocarcinoma cell lines. CD39 was identified as an independent poor prognostic factor in cholangiocarcinoma. In addition, in vitro and in vivo data indicated that the knockdown of CD39 could suppress the proliferation, migration, and invasion ability. The opposite results were observed when CD39 was overexpressed. Mechanistically, CD39 could bind with Annexin A2 (ANXA2), which influences the phosphorylation level of ANXA2 at the Tyr24 site, thereby promoting the activation of PI3K/AKT signaling, which resulted in the biological change in cholangiocarcinoma.

Conclusion CD39 was identified as an independent prognostic factor of poor overall survival for patients with cholangiocarcinoma. In terms of the biological role of CD39, our data indicated that CD39 promoted the progression and metastasis of cholangiocarcinoma through binding with ANXA2, and through activating the PI3K/AKT signaling. In brief, CD39 is a potential prognostic factor and therapeutical target for cholangiocarcinoma.