通过分析血清明胶酶水平鉴别自身免疫性胰腺炎与胰腺癌

Differential Diagnosis of Autoimmune Pancreatitis From Pancreatic Cancer by Analysis of Serum Gelatinase Levels.

作者信息

Felix Klaus, Dobiasch Sophie, Gaida Matthias M, Schneider Kathrin, Werner Jens, Martens Erik, Vandooren Jennifer, Opdenakker Ghislain

机构信息

From the *Department of General Surgery and †Institute of Pathology, University of Heidelberg, Heidelberg; and ‡Department of General, Visceral, Transplantations, Vascular and Thorax Surgery, LMU Munich, Munich, Germany; and §Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

出版信息

Pancreas. 2016 Aug;45(7):1048-55. doi: 10.1097/MPA.0000000000000576.

DOI:10.1097/MPA.0000000000000576

PMID:26692441

Abstract

OBJECTIVES

The aim of this study was to analyze serum gelatinases as part of the clinical strategy for the preoperative differentiation between autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). The finding of differential markers will prevent unnecessary surgical resection and allow optimal treatment of these diseases.

METHODS

Quantitative gelatin zymography was applied to analyze all individual gelatinase forms in serum and to define proteinase alterations associated with AIP and PDAC. For this purpose, sera of 130 patients, being 29 with AIP, 33 with chronic pancreatitis, 32 with PDAC, and 36 healthy controls, were first assayed for gelatinase levels by quantitative zymography before further validation by the analysis with commercial sandwich enzyme linked immunosorbent assays.

RESULTS

Serum profiling data obtained by zymography analysis revealed that gelatinase B/matrix metalloproteinase 9 (MMP-9), the neutrophil gelatinase B-associated lipocalin/MMP-9 complex, and gelatinase A/MMP-2 levels were significantly increased in patients with AIP. These proteins are promising markers to discriminate between AIP and PDAC. The best composite parameter, being the ratio of total MMP-9 over MMP-2 levels, can predict 93% of the AIP and 75% of the PDAC correctly. With enzyme linked immunosorbent assay, we confirmed the zymography results.

CONCLUSIONS

Differential gelatinase serum profiles as AIP markers, together with other clinical tests, help to assure the diagnosis of PDAC or AIP.

摘要

目的

本研究旨在分析血清明胶酶，作为自身免疫性胰腺炎（AIP）与胰腺导管腺癌（PDAC）术前鉴别临床策略的一部分。鉴别标志物的发现将避免不必要的手术切除，并使这些疾病得到最佳治疗。

方法

应用定量明胶酶谱法分析血清中所有个体明胶酶形式，并确定与AIP和PDAC相关的蛋白酶改变。为此，首先通过定量酶谱法检测130例患者的血清明胶酶水平，这些患者包括29例AIP患者、33例慢性胰腺炎患者、32例PDAC患者和36例健康对照，然后通过商业夹心酶联免疫吸附测定法进行进一步验证。

结果

酶谱分析获得的血清谱数据显示，AIP患者血清中的明胶酶B/基质金属蛋白酶9（MMP-9）、中性粒细胞明胶酶B相关脂质运载蛋白/MMP-9复合物和明胶酶A/MMP-2水平显著升高。这些蛋白质是区分AIP和PDAC的有前景的标志物。最佳综合参数，即总MMP-9与MMP-2水平之比，能够正确预测93%的AIP和75%的PDAC。通过酶联免疫吸附测定法，我们证实了酶谱分析结果。