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胸腔积液的多重可溶性生物标志物分析。

Multiplex Soluble Biomarker Analysis from Pleural Effusion.

机构信息

Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Huddinge University Hospital, SE-14186 Stockholm, Sweden.

Karolinska University Hospital, Karolinska University laboratory, Huddinge University Hospital, SE-14186 Stockholm, Sweden.

出版信息

Biomolecules. 2020 Jul 28;10(8):1113. doi: 10.3390/biom10081113.

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.

摘要

恶性胸膜间皮瘤(MPM)是一种高度侵袭性和治疗抵抗的胸膜恶性肿瘤,由石棉暴露引起。MPM 预后不良,患者生存时间短。肿瘤的亚型强烈影响生存时间。呼吸困难和胸腔积液积聚是 MPM 的常见症状。使用组织病理学或细胞学进行与其他恶性肿瘤和反应性疾病的鉴别诊断,始终辅以免疫组织化学,有时还辅以胸腔积液上清液中可溶性生物标志物的分析。我们通过 Luminex 多重分析评估了可溶性血管生成相关分子作为 MPM 的可能预后和诊断生物标志物。分析了 42 例恶性胸膜间皮瘤(MPM)、36 例腺癌(AD)和 40 例良性(BE)胸腔积液患者的胸腔积液,以分析 10 种不同的分析物,这些分析物在之前的研究中与血管生成有关,包括血管生成素-1、HGF、MMP-7、骨桥蛋白、TIMP-1、半乳糖凝集素、间皮素、NRG1-b1、黏附素-1(SDC-1)和 VEGF,采用人预混多分析物 Luminex 试剂盒。我们发现,与腺癌相比,恶性间皮瘤胸腔积液中的可溶性 SDC-1 和 MMP-7 水平显著降低,而间皮素和半乳糖凝集素-1 水平显著升高。与良性样本相比,恶性胸膜间皮瘤胸腔积液中的 Galectin-1、HGF、Mesothelin、MMP-7、Osteopontin、shed SDC-1、NRG1-β1、VEGF 和 TIMP-1 明显升高。此外,恶性病例胸腔积液中 Mesothelin 与 shed SDC-1 呈负相关,VEGF、Angiopoietin-1 与 shed SDC-1 水平呈正相关。胸腔积液中 SDC-1 和 VEGF 的水平对恶性间皮瘤患者具有预后价值。综上所述,我们的数据表明,MMP-7、shed SDC-1、间皮素和半乳糖凝集素-1可作为 MPM 患者的诊断标志物,而 VEGF 和 SDC-1 可作为预后标志物。此外,Galectin-1、HGF、Mesothelin、MMP-7、Osteopontin、shed SDC-1 和 TIMP-1 可用于恶性病例的诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aba/7464384/d89ce3bcc9e1/biomolecules-10-01113-g001.jpg

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