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

IF 3.9 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Hepatology Research Pub Date : 2024-03-02 DOI:10.1111/hepr.14031

Xuefeng Li, Yukinori Koyama, Kojiro Taura, Takahiro Nishio, Tomoaki Yoh, Hiroto Nishino, Yusuke Uemoto, Yusuke Kimura, Daichi Nakamura, Nguyen Hai Nam, Motohiko Sato, Satoru Seo, Keiko Iwaisako, Etsuro Hatano

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Abstract

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.

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自体表皮生长因子的高表达与胆管癌患者无复发生存率低有关

背景和目的Autotaxin（ATX）是一种细胞外溶血磷脂酶D，可催化溶血磷脂酰胆碱水解为溶血磷脂酸（LPA）。最近不断积累的证据表明，ATX 在恶性肿瘤中具有生物学作用。本研究采用免疫组化方法评估了 ATX 在 97 例人类 CCA 组织中的表达。测定了 CCA 患者（26 人）和健康人（8 人）的血清 ATX 水平。结果CCA组织中ATX的高表达与淋巴结转移的高频率显著相关（p = 0.050）。与低 ATX 表达相比，高 ATX 表达与较短的总生存期（p = 0.032）和无复发生存期（RFS）（p = 0.001）相关。在多变量Cox分析中，ATX高表达（p = 0.019）是导致RFS缩短的独立因素。与低ATX表达相比，高ATX表达与较高的Ki-67阳性细胞数明显相关（p <0.001）。男性 CCA 患者的血清 ATX 水平明显高于健康男性（p = 0.030）。在 CCA 的肿瘤微环境中，ATX 蛋白主要在肿瘤细胞、癌相关成纤维细胞、浆细胞和胆道上皮细胞中表达。

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来源期刊

Hepatology Research 医学-胃肠肝病学

CiteScore

8.30

自引率

14.30%

发文量

124

审稿时长

1 months

期刊介绍： Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.