[腹膜后纤维化：用于诊断和治疗监测的生物标志物谱的开发]

[Retroperitoneal fibrosis: development of a biomarker profile for diagnosis and therapy monitoring].

作者信息

Kukuk S, Kretschmer A, Bruck H, Roth S, Brandt A S

机构信息

Klinik für Urologie und Kinderurologie, Helios Klinikum Wuppertal, Zentrum für Forschung in der klinischen Medizin (ZFKM), Lehrstuhl der Universität Witten/Herdecke, Heusnerstraße 40, 42285, Wuppertal, Deutschland,

出版信息

Urologe A. 2015 Jan;54(1):52-61. doi: 10.1007/s00120-014-3713-z.

DOI:10.1007/s00120-014-3713-z

PMID:25503722

Abstract

INTRODUCTION

Retroperitoneal fibrosis (RPF) is a rare chronic inflammatory disease which is characterized by fibrotic tissue in the retroperitoneal space. There have only been a few studies on serum markers of this disease. The main goal of the current investigation was to identify biological markers which are increased in the serum of patients suffering from RPF and which may correlate with the extent of fibrosis.

MATERIAL AND METHODS

The serum of 42 patients with primary and yet untreated retroperitoneal fibrosis was examined for biomarkers known to be specific for fibrotic diseases and compared to a control group. In addition, patients were stratified according to the extent and volume of the retroperitoneal mass using cross-sectional imaging. To estimate the discriminatory power of the evaluated biomarkers, receiver operating characteristic (ROC) curves were created.

RESULTS

Independent of the extent of fibrosis, calprotectin, fibrinogen, osteopontin, matrix metallopeptidase 9 (MMP-9), tenascin C and TIMP metallopeptidase inhibitor 1 (TIMP-1) were significantly increased (p<0.01) in patients suffering from RPF compared to the control group. Connective tissue growth factor (CTGF) was significantly elevated (p<0.01) in patients with high RPF burden only but monocyte chemoattractant protein 1 (MCP-1) and heart-type fatty acid binding protein (H-FABP) showed no increase in serum levels. The discriminatory power of these parameters was ranked by the ROC analysis which demonstrated an area under the curve (AUC) >0.87 for MMP-9, TIMP-1, osteopontin, tenascin C, asymmetric dimethylarginine (ADMA), fibrinogen and calprotectin and an AUC <0.64 for MMP-2, CTGF, H-FABP and MCP-1.

CONCLUSION

Several biomarkers of fibrogenesis were significantly elevated in patients suffering from RPF as compared to a control group. These biomarker candidates will be further evaluated for their potential to allow a differentiation between other diseases or if they could be used for disease monitoring.

摘要

引言

腹膜后纤维化（RPF）是一种罕见的慢性炎症性疾病，其特征是腹膜后间隙出现纤维化组织。关于该疾病血清标志物的研究仅有少数几项。本研究的主要目的是确定在RPF患者血清中升高且可能与纤维化程度相关的生物标志物。

材料与方法

检测42例未经治疗的原发性腹膜后纤维化患者血清中的纤维化疾病特异性生物标志物，并与对照组进行比较。此外，使用横断面成像根据腹膜后肿块的范围和体积对患者进行分层。为评估所评价生物标志物的鉴别能力，绘制了受试者工作特征（ROC）曲线。

结果

与对照组相比，无论纤维化程度如何，RPF患者的钙卫蛋白、纤维蛋白原、骨桥蛋白、基质金属蛋白酶9（MMP-9）、腱生蛋白C和金属蛋白酶组织抑制因子1（TIMP-1）均显著升高（p<0.01）。仅在高RPF负荷患者中结缔组织生长因子（CTGF）显著升高（p<0.01），但单核细胞趋化蛋白1（MCP-1）和心型脂肪酸结合蛋白（H-FABP）血清水平未升高。通过ROC分析对这些参数的鉴别能力进行排序，结果显示MMP-9、TIMP-1、骨桥蛋白、腱生蛋白C、不对称二甲基精氨酸（ADMA）、纤维蛋白原和钙卫蛋白的曲线下面积（AUC）>0.87，而MMP-2、CTGF、H-FABP和MCP-1的AUC<0.64。