Identification of novel autoantibodies for detection of malignant mesothelioma.

Identification of novel autoantibodies for detection of malignant mesothelioma.
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DOI:
10.1371/journal.pone.0072458
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhong L
Zhong L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang X;Shen W;Dong X;Fan J;Liu L;Gao X;Kernstine KH;Zhong L

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恶性间皮瘤(MM)的存活率一直受到缺乏有效和准确的早期检测方法的阻碍。免疫系统可能通过产生与肿瘤相关的自身抗体来检测肿瘤进展的早期变化。因此,在本研究中,我们将对肿瘤蛋白的体液免疫反应转化为对MM的潜在血液试验。利用MM肿瘤组织构建了T7噬菌体MM cDNA文库,并使用MM患者和正常血清样本进行了肿瘤相关抗原(TAAs)的活组织扫描。对来自生物扫描文库的约1008个噬菌体TAA克隆进行蛋白质芯片构建,并以53份MM和52份对照血清样本作为训练组进行测试。用TCLASS系统和Logistic回归统计分析从训练组中筛选出9个候选自身抗体标志物,在受试者工作特性分析中获得94.3%的敏感性和90.4%的特异性,AUC值为0.89。以50例患者和50例正常血清作为独立盲法验证,AUC为0.82,灵敏度和特异度分别为86.0%和86.0%。序列测定和BLASTN分析表明,这9个候选标记中有5个与肿瘤相关蛋白(PDIA6、MEG3、SDCCAG3、IGHG3、IGHG1)有很强的同源性。我们的结果表明,使用一组9个自身抗体标记物检测多发性骨髓瘤具有良好的准确性。尽管这些结果需要在高危人群中进一步验证,但它们为开发一种基于血清的多发性骨髓瘤诊断方法提供了潜力。
The malignant mesothelioma (MM) survival rate has been hampered by the lack of efficient and accurate early detection methods. The immune system may detect the early changes of tumor progression by responding with tumor-associated autoantibody production. Hence, in this study, we translated the humoral immune response to cancer proteins into a potential blood test for MM. A T7 phage MM cDNA library was constructed using MM tumor tissues and biopanned for tumor-associated antigens (TAAs) using pooled MM patient and normal serum samples. About 1008 individual phage TAA clones from the biopanned library were subjected to protein microarray construction and tested with 53 MM and 52 control serum samples as a training group. Nine candidate autoantibody markers were selected from the training group using Tclass system and logistic regression statistical analysis, which achieved 94.3% sensitivity and 90.4% specificity with an AUC value of 0.89 in receiver operating characteristic analysis. The classifier was further evaluated with 50 patient and 50 normal serum samples as an independent blind validation, and the sensitivity of 86.0% and the specificity of 86.0% were obtained with an AUC of 0.82. Sequencing and BLASTN analysis of the classifier revealed that five of these nine candidate markers were found to have strong homology to cancer related proteins (PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1). Our results indicated that using a panel of 9 autoantibody markers presented a promising accuracy for MM detection. Although the results need further validation in high-risk groups, they provided the potentials in developing a serum-based assay for MM diagnosis.
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发表时间: 2009-04
期刊: Translational research : the journal of laboratory and clinical medicine
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作者:
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通讯作者: Kamp DW
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发表时间: 1992-12-02
影响因子: 6.4
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DOI: 10.1016/j.lungcan.2008.02.012
发表时间: 2008-10-01
期刊: LUNG CANCER
影响因子: 5.3
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