BACKGROUND & AIMS Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery. METHODS Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data. RESULTS Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival. CONCLUSIONS Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.

中文翻译：

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循环骨桥蛋白水平升高与胆管癌切除术后生存率低有关

背景和目的 胆管癌 (CCA) 是一种原发性肝脏恶性肿瘤，其发病率和死亡率在全球范围内不断上升。手术治疗仍然是唯一可能治愈的治疗选择，但目前尚不清楚哪些患者从扩大肝脏手术中获益最多，这突出了新的术前分层策略的必要性。骨桥蛋白是一种分泌的细胞外糖磷蛋白，与炎症、代谢紊乱和癌症有关。在这里，我们检查了循环骨桥蛋白血清水平作为接受扩大肝脏手术的 CCA 患者的诊断或预后生物标志物的潜力。方法 使用半定量逆转录酶 PCR 和免疫组织化学分析人和鼠 CCA 肿瘤样本中的骨桥蛋白表达水平。107 名接受选择性肿瘤切除术的 CCA 患者和 55 名健康对照者通过酶联免疫吸附试验测量骨桥蛋白血清浓度。结果与临床数据相关。结果 与 CCA 肿瘤细胞和肿瘤基质的上调相关，与健康对照和原发性硬化性胆管炎患者相比，胆管癌患者的血清骨桥蛋白水平升高。重要的是，术前和术后骨桥蛋白的升高与术后生存率低显着相关。结论 血清骨桥蛋白浓度代表了可切除 CCA 患者的有希望的预后生物标志物，有助于指导术前治疗决策，并确定将特别受益于扩大肝脏手术的患者。小结：扩大肝脏手术是胆管癌（CCA/胆管癌）患者唯一可能治愈的治疗方法，但目前尚不清楚哪些患者从手术中获益最大。在 CCA 患者中检测骨桥蛋白（一种参与多种人类疾病的特定分泌糖蛋白）的血清水平可能有助于识别那些特别受益于肿瘤切除术的患者。