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A multiplex immunoassay of serum biomarkers for the detection of uveal melanoma.
Clinical Proteomics ( IF 2.8 ) Pub Date : 2019-03-05 , DOI: 10.1186/s12014-019-9230-8
Jin Song 1, 2 , Shannath L Merbs 3 , Lori J Sokoll 1 , Daniel W Chan 1 , Zhen Zhang 1
Affiliation  

Background Approximately 50% of uveal melanoma (UM) patients develop metastases preferentially in the liver leading to death within 15 months. Currently, there is no effective treatment for metastatic UM, in part because the tumor burden is typically high when liver metastases are detected through abnormal liver function tests (LFTs) or imaging studies. The use of LFTs results followed by diagnostic tests has high specificity and predictive values but low sensitivity, and better tests are needed for early diagnosis of the primary tumor as well as its metastatic spread. To evaluate serum biomarkers for the early detection of UM, multiplex immunoassays were developed. Methods Magnetic bead-based multiplex immunoassays were developed for the selected serum biomarkers using a Bio-Plex 200 system. The dynamic ranges, lower limits of detection and quantification, cross-reactivity, and intra- and inter-assay precision were assessed. All proteins were analyzed in sera of 48 patients diagnosed with UM (14 metastatic, 9 disease-free (DF) ≥ 5 years, 25 unknown) and 36 healthy controls. The performance of the biomarkers was evaluated individually and in combination for their ability to detect UM. Results A 7-plex immunoassay of OPN, MIA, CEACAM-1, MIC-1, SPON1, POSTN and HSP27 was developed with negligible cross-reactivity, recovery of 84-105%, and intra-assay and inter-assay precision of 2.3-7.5% or 2.8-20.8%, respectively. Logistic regression identified a two-marker panel of HSP27 and OPN that significantly improved the individual biomarker performance in discriminating UM from healthy controls. The improved discrimination of a two-marker panel of MIA and MIC-1 was also observed between metastatic UM and DF, however not statistically significant due to the small sample size. Conclusions The multiplex immunoassay provides sufficient analytical performance to evaluate serum biomarkers that complement each other in detection of UM, and warrants further validation with a larger number of patient samples.

中文翻译:

用于检测葡萄膜黑色素瘤的血清生物标志物的多重免疫测定。

背景 大约 50% 的葡萄膜黑色素瘤 (UM) 患者优先在肝脏中发生转移,导致在 15 个月内死亡。目前,转移性 UM 没有有效的治疗方法,部分原因是当通过异常肝功能测试 (LFT) 或影像学研究检测到肝转移时,肿瘤负荷通常很高。使用 LFTs 结果后进行诊断测试具有较高的特异性和预测价值,但敏感性较低,需要更好的测试来早期诊断原发性肿瘤及其转移扩散。为了评估用于早期检测 UM 的血清生物标志物,开发了多重免疫测定法。方法 使用 Bio-Plex 200 系统针对选定的血清生物标志物开发基于磁珠的多重免疫测定。动态范围,评估了检测和定量的下限、交叉反应性以及测定内和测定间的精密度。对 48 名诊断为 UM 的患者(14 名转移性患者,9 名无病 (DF) ≥ 5 年,25 名未知)和 36 名健康对照者的血清中的所有蛋白质进行了分析。对生物标志物的性能进行了单独和组合评估,以确定它们检测 UM 的能力。结果 开发了 OPN、MIA、CEACAM-1、MIC-1、SPON1、POSTN 和 HSP27 的 7 重免疫测定,交叉反应可忽略不计,回收率为 84-105%,测定内和测定间精度为 2.3分别为 -7.5% 或 2.8-20.8%。逻辑回归确定了 HSP27 和 OPN 的两个标志物组,显着提高了个体生物标志物在区分 UM 与健康对照方面的表现。在转移性 UM 和 DF 之间也观察到 MIA 和 MIC-1 的两个标志物组的区分度提高,但由于样本量小,没有统计学意义。结论 多重免疫测定提供了足够的分析性能来评估在检测 UM 中相互补充的血清生物标志物,并需要用更多的患者样本进行进一步验证。
更新日期:2020-04-22
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