Examination of oral cancer biomarkers by tissue microarray analysis
Examination of oral cancer biomarkers by tissue microarray analysis
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DOI：
10.1001/archotol.134.5.539
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Chen, Chu
中科院分区：
文献类型：
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作者：
Choi, Peter;Jordan, C. Diana;Chen, Chu
目的：为了验证一个子集的基因，可以潜在地作为生物标志物的口腔鳞状细胞癌（OSCC）的DNA微阵列结果，通过检查他们的表达与替代的定量方法，并通过评估其蛋白质levels.Design：基于我们的实验室和文献中报道的数据的DNA微阵列数据，我们确定了6个潜在的生物标志物的OSCC进一步调查。应用实时荧光定量聚合酶链反应技术检测口腔鳞癌组织和正常口腔黏膜组织中CDH11、MMP 3、TGF β 1、TGF β 1、TGF β 2、TGF β 1、TGF β 2、TGF β 3的表达变化。我们进一步研究了有效的标志物在蛋白质水平的免疫组化分析OSCC组织芯片section.Results：定量实时聚合酶链反应分析显示上调CDH11，CD4+，PO4+，和TNC基因的表达和减少TGM3的表达在OSCC组织与对照组织相比，MMP 3没有发现差异表达。在组织微阵列免疫组织化学分析中，与对照组织相比，分泌蛋白（分泌蛋白，酸性，富含半胱氨酸），骨膜蛋白和腱生蛋白C在肿瘤组织中表现出增加的蛋白表达，并且它们的表达主要定位于肿瘤相关基质而不是肿瘤上皮。相反，转氨酶3蛋白的表达被发现只在角质形成细胞在控制组织中，并显着下调在癌cells.Conclusions：6个潜在的基因标记的口腔鳞癌，最初确定的DNA微阵列分析，差异表达的CDH11，CDH，POR4，TNC和TGM3的定量实时聚合酶链反应进行了验证。组织芯片免疫组化分析清楚地显示了由p53、p53、TNC和TGM3编码的蛋白质的差异表达和定位。
Objective: To validate the DNA microarray results on a subset of genes that could potentially serve as biomarkers of oral squamous cell carcinoma (OSCC) by examining their expression with an alternate quantitative method and by assessing their protein levels.Design: Based on DNA microarray data from our laboratory and data reported in the literature, we identified 6 potential biomarkers of OSCC to investigate further. We used quantitative real-time polymerase chain reaction to examine expression changes of CDH11, MMP3, SPARC, POSTN, TNC, and TGM3 in OSCC and histologically normal control tissues. We further examined validated markers at the protein level by immunohistochemical analysis of OSCC tissue microarray sections.Results: Quantitative real-time polymerase chain reaction analysis revealed upregulation of CDH11, SPARC, POSTN, and TNC gene expression and decreased TGM3 expression in OSCC tissue compared with control tissue; MMP3 was not found to be differentially expressed. In tissue microarray immunohistochemical analyses, SPARC (secreted protein, acidic, rich in cysteine), periostin, and tenascin C exhibited increased protein expression in tumor tissue compared with control tissue, and their expression was primarily localized within tumor-associated stroma rather than tumor epithelium. Conversely, transglutaminase 3 protein expression was found only within keratinocytes in control tissue and was significantly downregulated in cancer cells.Conclusions: Of 6 potential gene markers of OSCC, initially identified by DNA microarray analyses, differential expression of CDH11, SPARC, POSTN, TNC, and TGM3 were validated by quantitative real-time polymerase chain reaction. Differential expression and localization of proteins encoded by SPARC, POSTN, TNC, and TGM3 were clearly shown by tissue microarray immunohistochemical analysis.