Ocular Mucin Gene Expression Levels as Biomarkers for the Diagnosis of Dry Eye Syndrome
Ocular Mucin Gene Expression Levels as Biomarkers for the Diagnosis of Dry Eye Syndrome
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DOI：
10.1167/iovs.11-7655
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Calonge, Margarita
中科院分区：
文献类型：
--
作者：
Corrales, Rosa M.;Narayanan, Srihari;Calonge, Margarita
目的。评估中度至重度干眼综合征（DES）患者结膜印象细胞学样本中眼黏液MUC1、MUC2、MUC4、MUC5AC和MUC7 mRNA水平，并与健康人群进行比较；并研究将这些粘蛋白基因水平作为DES的生物标志物，随后作为DES的潜在诊断测试。这项前瞻性研究开始于2000年，结束于2009年。38名DES患者和43名年龄和性别匹配的健康受试者完成了研究的初始部分。在后期对16名健康受试者和30名DES患者进行重复调查，作为外部验证数据。对所有受试者进行结膜印象细胞学检查，检测眼黏液蛋白基因MUC1、MUC2、MUC4、MUC5AC和MUC7的基因表达。统计学分析两组受试者黏液蛋白基因表达水平是否存在差异。计算黏液蛋白基因表达对DES诊断的敏感性和特异性。与正常人相比，DES患者结膜上皮MUC1、MUC2、MUC4、MUC5AC的表达均显著降低（P < 0.0001）。这些结果在外部对照受试者和患者组中也得到了重复。MUC1表达水平在所有检测基因中具有最高的敏感性（83.3%）和特异性（87.5%）。这些数据强烈提示MUC1的表达水平可以作为DES的诊断测试，用于研究性和选择性临床试验。（Invest Ophthalmol Vis Sci. 2011;52:8363-8369） DOI: 10.1167/iovs.11-7655
PURPOSE. To evaluate mRNA levels of the ocular mucins MUC1, MUC2, MUC4, MUC5AC, and MUC7 in conjunctival impression cytology samples from patients with moderate to severe dry eye syndrome (DES) compared with a population of healthy subjects; and to investigate the use of the levels of these mucin genes as biomarkers of DES and subsequently as a potential diagnostic test for DES.METHODS. This prospective study commenced in the year 2000 and ended in the year 2009. Thirty-eight patients with DES and 43 age-and sex-matched healthy subjects completed the initial part of the study. Investigations were repeated at a later stage in 16 healthy subjects and 30 patients with DES, which were used as external validation data. Conjunctival impression cytology was performed in all subjects to test gene expression of ocular mucin genes MUC1, MUC2, MUC4, MUC5AC, and MUC7. Statistical analysis was performed to determine whether there was a difference in the levels of mucin gene expression between the two groups of subjects. Sensitivity and specificity of mucin gene expression for the diagnosis of DES was calculated.RESULTS. Expressions of MUC1, MUC2, MUC4, and MUC5AC (P < 0.0001) were significantly lower in conjunctival epithelium of patients with DES compared with that in normal subjects. These results were replicated in the external control subject and patient groups. MUC1 expression levels demonstrated the greatest sensitivity (83.3%) and specificity (87.5%) among all genes tested.CONCLUSIONS. The data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials. (Invest Ophthalmol Vis Sci. 2011;52:8363-8369) DOI: 10.1167/iovs.11-7655