High expression of autotaxin is associated with poor recurrence‐free survival in cholangiocarcinoma

• Published in: Hepatology research Vol. 54; no. 9; pp. 817 - 826
• Main Authors: Li, Xuefeng, Koyama, Yukinori, Taura, Kojiro, Nishio, Takahiro, Yoh, Tomoaki, Nishino, Hiroto, Uemoto, Yusuke, Kimura, Yusuke, Nakamura, Daichi, Nam, Nguyen Hai, Sato, Motohiko, Seo, Satoru, Iwaisako, Keiko, Hatano, Etsuro
• Format: Journal Article
• Language: English
• Published: Netherlands Wiley Subscription Services, Inc 01.09.2024
• Subjects: autotaxin; Cholangiocarcinoma; Epithelial cells; Immunofluorescence; Immunohistochemistry; Ki‐67; Lymph nodes; Lysophosphatidic acid; lysophosphatidic acid receptor; Lysophosphatidylcholine; Lysophospholipase; Metastases; Plasma cells; Tumor cells; Tumor microenvironment; Tumors; Ki-67; lysophosphatidic acid receptor; autotaxin; cholangiocarcinoma
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.14031

Background and Aim Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. Methods In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. Results High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence‐free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki‐67‐positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer‐associated fibroblasts, plasma cells, and biliary epithelial cells. Conclusions Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA.