Background and AimAutotaxin (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.MethodsIn 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.ResultsHigh 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.ConclusionsOur study highlights the clinical evidence and independent prognostic value of ATX in human CCA.

中文翻译：

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自分泌运动因子的高表达与胆管癌无复发生存率差相关

背景和目标自分泌运动因子(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)。最近越来越多的证据表明 ATX 在恶性肿瘤中的生物学作用。然而，ATX在人胆管癌(CCA)中的表达和临床意义仍不清楚。方法在本研究中，通过免疫组织化学方法评估了97例人CCA组织中ATX的表达。测定 CCA 患者的血清 ATX 水平（n= 26) 和健康受试者 (n= 8）。自分泌运动因子通过免疫荧光染色来表征肿瘤微环境内细胞类型的表达。结果 CCA 组织中 ATX 的高表达与淋巴结转移的较高频率显着相关（p= 0.050）。高 ATX 表达与较短的总生存期相关（p= 0.032）和无复发生存率（RFS）（p= 0.001) 低于 ATX 表达。在多变量 Cox 分析中，ATX 高表达（p= 0.019）是较短 RFS 的独立因素。与低 ATX 表达相比，高 ATX 表达与较高的 Ki-67 阳性细胞计数显着相关（p< 0.001）。男性 CCA 患者的血清 ATX 水平显着高于健康男性受试者（p= 0.030）。在CCA的肿瘤微环境中，ATX蛋白主要在肿瘤细胞、癌症相关成纤维细胞、浆细胞和胆管上皮细胞中表达。结论我们的研究强调了ATX在人类CCA中的临床证据和独立预后价值。