Genomic biomarkers in chronic beryllium disease and sarcoidosis.
Genomic biomarkers in chronic beryllium disease and sarcoidosis.
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DOI：
10.1016/j.rmed.2021.106390
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发表时间：
2021-10
影响因子：
4.3
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Lin NW;Maier LA;Mroz MM;Jacobson S;MacPhail K;Liu S;Lei Z;Barkes BQ;Fingerlin TE;Hamzeh N;Mayer AS;Restrepo CI;Chhabra D;Yang IV;Li L
背景以往的基因表达研究已证实干扰素γ、肿瘤坏死因子α、核糖核酸酶3、CXCL9和CD55基因是结节病和/或慢性铍病的潜在生物标志物。我们假设这些基因的差异表达可以作为结节病和CBD的诊断生物标记物，以及结节病的预后生物标记物。研究设计/方法我们对CBD患者(n=132)、铍致敏(BES)患者(n=109)、结节病患者(n=99)和正常对照(n=997)的全血标本进行RT-qPCR，以确定靶基因的差异表达。然后，我们进行Logistic回归建模，并生成ROC曲线，以确定哪些基因可以最准确地区分：1)CBD与结节病；2)CBD与BES；3)结节病与对照组；4)非进展性与进行性结节病。结果与结节病组相比，结节病组CD55和肿瘤坏死因子α表达显著上调，而CXCL9表达显著下调(P<0.05)。Logistic回归模型的ROC曲线显示CD5 5、肿瘤坏死因子α和CXCL9联合应用对区分胆管疾病和结节病具有很高的鉴别能力，AUC值为0.98。与对照组相比，结节病患者CD55和肿瘤坏死因子α的表达显著下调(P<0.05)。模型的ROC曲线显示CD5 5和肿瘤坏死因子α对结节病和对照组有较好的区分能力，AUC值为0.86。没有可以准确区分CBD和BES或结节病表型的基因组合。CD55、肿瘤坏死因子α和CXCL9的表达水平可以准确地区分胆管疾病和结节病，而CD55和肿瘤坏死因子α的表达水平可以准确地区分结节病和对照组。
Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes. We then performed logistic regression modeling and generated ROC curves to determine which genes could most accurately differentiate: 1) CBD versus sarcoidosis 2) CBD versus BeS 3) sarcoidosis versus controls 4) non-progressive versus progressive sarcoidosis. Results CD55 and TNFα were significantly upregulated, while CXCL9 was significantly downregulated in CBD compared to sarcoidosis (p < 0.05). The ROC curve from the logistic regression model demonstrated high discriminatory ability of the combination of CD55, TNFα, and CXCL9 to distinguish between CBD and sarcoidosis with an AUC of 0.98. CD55 and TNFα were significantly downregulated in sarcoidosis compared to controls (p < 0.05). The ROC curve from the model showed a reasonable discriminatory ability of CD55 and TNFα to distinguish between sarcoidosis and controls with an AUC of 0.86. There was no combination of genes that could accurately differentiate between CBD and BeS or sarcoidosis phenotypes. Interpretation CD55, TNFα and CXCL9 expression levels can accurately differentiate between CBD and sarcoidosis, while CD55 and TNFα expression levels can accurately differentiate sarcoidosis and controls.
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DOI：
10.1164/rccm.200912-1855oc
发表时间：
2010-06-15
影响因子：
24.7
作者：
Lockstone, Helen E.;Sanderson, Sharon;Ho, Ling-Pei
通讯作者：
Ho, Ling-Pei
DOI：
10.1084/jem.184.3.963
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher M;Gerber B;Loetscher P;Jones SA;Piali L;Clark-Lewis I;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
5.8
作者：
Beijer, E.;Meek, B.;Veltkamp, M.
通讯作者：
Veltkamp, M.
DOI：
10.1164/rccm.202002-0251st
发表时间：
2020-04-15
影响因子：
24.7
作者：
Crouser, Elliott D.;Maier, Lisa A.;Baughman, Robert P.
通讯作者：
Baughman, Robert P.
影响因子：
24.3
作者：
Maier, LA;Sawyer, RT;Newman, LS
通讯作者：
Newman, LS