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中性粒细胞明胶酶相关脂质运载蛋白作为肝门周围胆管癌的治疗诊断标志物

Neutrophil Gelatinase-associated Lipocalin as a Theragnostic Marker in Perihilar Cholangiocarcinoma.

作者信息

Nair Amit, Ingram Nicola, Verghese Eldo T, Wijetunga Imeshi, Markham Alex F, Wyatt Judy, Prasad K Rajendra, Coletta P Louise

机构信息

Section of Molecular Gastroenterology, Leeds Institute of Medical Research, University of Leeds, Leeds, U.K.

Department of Histopathology, St. James's University Hospital, Leeds, U.K.

出版信息

Anticancer Res. 2018 Dec;38(12):6737-6744. doi: 10.21873/anticanres.13043.

Abstract

BACKGROUND/AIM: Platforms using valid molecular targets can provide concurrent diagnostic and treatment (theragnostic) options in perihilar cholangiocarcinoma (PHC). Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker in the biliary secretome of PHC. Its potential as a theragnostic target and its prognostic significance in this cancer was, therefore, explored.

MATERIALS AND METHODS

In-vitro studies were used to determine NGAL localization in several cholangiocarcinoma cell lines. Tissue expression of NGAL was quantified in PHC resection cases from 2000-2010 by immunohistochemistry.

RESULTS

NGAL was expressed in the majority of tested cell lines and localized to their membranes. Tissues from 54 patients underwent NGAL immunohistochemistry. Median tumoral NGAL expression was significantly higher than that in matched liver controls (p<0.001). Higher NGAL tumor expression was associated with nodal metastasis (p=0.021), although no significant association with survival was observed.

CONCLUSION

The expression and localization of NGAL in PHC make it a valid candidate biomarker for exploitation in theragnostic platforms.

摘要

背景/目的:使用有效分子靶点的平台可为肝门部胆管癌(PHC)提供同步诊断和治疗(诊疗一体化)方案。中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是PHC胆汁分泌组中的一种生物标志物。因此,探讨了其作为诊疗靶点的潜力及其在该癌症中的预后意义。

材料与方法

采用体外研究确定NGAL在几种胆管癌细胞系中的定位。通过免疫组织化学对2000年至2010年PHC切除病例中NGAL的组织表达进行定量分析。

结果

NGAL在大多数测试细胞系中表达,并定位于细胞膜。对54例患者的组织进行了NGAL免疫组织化学检测。肿瘤组织中NGAL的中位表达显著高于配对的肝脏对照(p<0.001)。虽然未观察到NGAL肿瘤表达与生存之间存在显著关联,但较高的NGAL肿瘤表达与淋巴结转移相关(p=0.021)。

结论

NGAL在PHC中的表达和定位使其成为诊疗一体化平台中可利用的有效候选生物标志物。

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