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MiRNA-196b、LCN2和TIMP1的组合是用于筛查家族性胰腺癌风险个体的一组潜在循环生物标志物。

The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer.

作者信息

Bartsch Detlef K, Gercke Norman, Strauch Konstantin, Wieboldt Ronja, Matthäi Elvira, Wagner Vinona, Rospleszcz Susanne, Schäfer Agnes, Franke Frederike S, Mintziras Ioannis, Bauer Christian, Grote Tobias, Figiel Jens, Di Fazio Pietro, Burchert Andreas, Reinartz Silke, Pogge von Strandmann Elke, Klöppel Günter, Slater Emily P

机构信息

Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, D-35043 Marburg, Germany.

Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Faculty of Medicine, Ludwig-Maximilians-Universität, Marchioninistr. 15, D-81377 Munich, Germany.

出版信息

J Clin Med. 2018 Sep 20;7(10):295. doi: 10.3390/jcm7100295.

Abstract

Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, = 50), FPC ( = 20), chronic pancreatitis ( = 10), IAR with relevant precursor lesions ( = 11) or non-relevant lesions ( = 5), 20 controls, and IAR with ( = 51) or without ( = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 ( = 144) enrichment and mutations ( = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels ( = 0.0007) and mutations in duodenal juice ( = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families.

摘要

家族性胰腺癌(FPC)的高危个体(IAR)是筛查的理想对象。不幸的是,目前尚无可靠的成像方式或生物标志物可用于检测高级别癌前病变或早期癌症。对218例个体的候选生物标志物LCN2、TIMP1、Glypican-1、RNU2-1f和miRNA-196b的循环水平进行了分析,这些个体包括散发性胰腺导管腺癌(PDAC,n = 50)、FPC(n = 20)、慢性胰腺炎(n = 10)、有相关前体病变的IAR(n = 11)或非相关病变的IAR(n = 5)、20例对照,以及胰腺成像有(n = 51)或无(n = 51)病变的IAR。此外,对相应的十二指肠液样本进行了Glypican-1(n = 144)富集和KRAS突变(n = 123)分析。miR-196b/LCN2/TIMP1组合能够以绝对的特异性和敏感性将高级别病变和I期PDAC与对照区分开来。相比之下,血清外泌体和十二指肠液中Glypican-1的富集并无诊断价值。12例PDAC患者中有9例在十二指肠液中检测到KRAS突变,而9例有相关前体病变的IAR中只有4例检测到。成像有病变的IAR中miR-196b/LCN2/TIMP1水平升高(P = 0.0007)和十二指肠液中KRAS突变(P = 0.0004)的情况明显比无成像病变的IAR更常见。miR-196b/LCN2/TIMP1组合可能是用于检测FPC家族IAR中高级别PDAC前体病变的有前景的生物标志物组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b4/6210952/d5d720da98e7/jcm-07-00295-g001.jpg

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