Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel.
Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel.
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DOI：
10.1371/journal.pone.0052021
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Rockson SG
中科院分区：
文献类型：
--
作者：
Lin S;Kim J;Lee MJ;Roche L;Yang NL;Tsao PS;Rockson SG
在我们先前的小鼠模型的转录谱分析中，我们已经确定了在水肿中具有改变的表达的显著少量的特定途径。在这项研究中，我们利用基于微阵列的人类皮肤的转录组学进行无偏的先验前瞻性候选识别，随后通过直接血清测定对这些候选进行验证。所得到的多分析物生物标志物组应灵敏地将人水肿受试者与正常个体区分开。我们招募了63名淋巴水肿受试者和27名正常人，试图发现可以区分患病个体和对照组的蛋白质分析物。为了最大限度地减少技术和生物学上不相关的变化，我们首先通过对从相同个体取样的成对患病和正常皮肤标本进行转录微阵列分析来确定潜在的候选者。我们将注意力集中在具有分泌的相应蛋白质产物的基因上，并将这些候选基因用于应用于患病和正常受试者的蛋白质多重测定。我们对最终的六种蛋白质组开发了一个基于逻辑回归的模型，并在一个单独的研究对象队列中验证了我们的系统。受试者工作特征曲线下面积计算为0.87（95% CI：0.75 - 0.97）。我们已经开发了一种准确的生物测定法，利用蛋白质代表四个中心的发病模式的疾病：淋巴管生成，炎症，纤维化，和脂质代谢，这表明这些蛋白质是直接相关的组织病理学在淋巴管功能不全的发病机制。进一步的研究是必要的，以确定是否这个新确定的生物标志物面板将具有实用性的工具，在体外诊断早期和潜伏性疾病，最终适用于风险分层，定量的疾病负担，并对治疗的反应可以很容易地设想。
In our previous transcriptional profiling of a murine model, we have identified a remarkably small number of specific pathways with altered expression in lymphedema. In this investigation, we utilized microarray-based transcriptomics of human skin for an unbiased a priori prospective candidate identification, with subsequent validation of these candidates through direct serum assay. The resulting multi-analyte biomarker panel sensitively should sensitively discriminate human lymphedema subjects from normal individuals. We enrolled 63 lymphedema subjects and 27 normals in our attempt to discover protein analytes that can distinguish diseased individuals from controls. To minimize technical and biologically irrelevant variation, we first identified potential candidates by performing transcriptional microarray analysis on paired diseased and normal skin specimens sampled from the same individuals. We focused our attention on genes with corresponding protein products that are secreted and took these candidates forward to a protein multiplex assay applied to diseased and normal subjects. We developed a logistic regression-based model on an eventual group of six proteins and validated our system on a separate cohort of study subjects. The area under the receiver operating characteristic curve was calculated to be 0.87 (95% CI : 0.75 to 0.97). We have developed an accurate bioassay utilizing proteins representing four central pathogenetic modalities of the disease: lymphangiogenesis, inflammation, fibrosis, and lipid metabolism, suggesting that these proteins are directly related to the pathogenesis of the tissue pathology in lymphatic vascular insufficiency. Further studies are warranted to determine whether this newly-identified biomarker panel will possess utility as an instrument for in vitro diagnosis of early and latent disease; the ultimate applicability to risk stratification, quantitation of disease burden, and response to therapy can easily be envisioned.
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影响因子：
37.8
作者：
Choi I;Lee S;Kyoung Chung H;Suk Lee Y;Eui Kim K;Choi D;Park EK;Yang D;Ecoiffier T;Monahan J;Chen W;Aguilar B;Lee HN;Yoo J;Koh CJ;Chen L;Wong AK;Hong YK
通讯作者：
Hong YK
影响因子：
6
作者：
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通讯作者：
Mehrara, Babak J.
影响因子：
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作者：
Ardigo, Diego;Assimes, Themistocles L.;Quertermous, Thomas
通讯作者：
Quertermous, Thomas
影响因子：
5.4
作者：
Choi, Inho;Lee, Sunju;Hong, Young-Kwon
通讯作者：
Hong, Young-Kwon
影响因子：
4.6
作者：
King, JY;Ferrara, R;Ashley, EA
通讯作者：
Ashley, EA