Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers
Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers
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DOI：
10.4161/cbt.8.1.7090
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发表时间：
2009-01-01
影响因子：
3.6
通讯作者：
Pandey, Akhilesh
中科院分区：
文献类型：
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作者：
Kashyap, Manoj Kumar;Marimuthu, Arivusudar;Pandey, Akhilesh
食管癌主要有两种类型，每种类型都有不同的病因和病理特征。食管鳞状细胞癌（ESCC）是食管癌的主要类型，占全球病例的近95%。虽然ESCC在发展中国家很普遍，但食管腺癌在发达国家很常见，通常与巴雷特食管有关。尽管ESCC的发病率较高，但尚未像食管腺癌那样深入研究。ESCC和食管腺癌是世界范围内常见的癌症，患者生存率较低，主要是因为这两种癌症都缺乏早期识别的生物标志物。对食管鳞状细胞癌发生和发展的分子机制仍知之甚少。DNA微阵列技术的发展使得癌症基因表达谱的高通量鉴定成为可能。为了确定早期诊断和/或治疗靶点的候选分子，我们使用全基因组DNA微阵列分析了20例ESCC的mRNA表达谱。与相应的邻近正常上皮相比，肿瘤中共有2235个基因被差异调控，其中881个基因被显著上调。我们通过组织微阵列和档案组织切片的免疫组化标记验证了两个先前未报道在ESCC中过表达的分子，即口腔癌过表达2 （ORAOV2）和成纤维细胞激活蛋白（FAP），并发现它们分别在98%（116/118）和68%（79/116）的病例中过表达。通过基因富集分析，我们发现花生四烯酸代谢途径中有几个基因显著下调。总的来说，使用这种方法，我们已经确定了一些有希望的新候选物，可以进一步验证它们作为ESCC生物标志物的潜力。
Cancer of the esophagus is of two main types, each with distinct etiological and pathological characteristics. Esophageal squamous cell carcinoma (ESCC) is predominant type of esophageal cancers worldwide comprising almost 95% of cases. While ESCC is prevalent in the developing world, esophageal adenocarcinoma is commonly seen in the developed country, usually in association with Barrett's esophagus. In spite of its higher prevalence, ESCC has not been studied as intensively as esophageal adenocarcinoma. ESCC and esophageal adenocarcinoma are common cancers worldwide with poor survival rate among patients mainly because both of these cancers lack early biomarkers of identification. Molecular mechanisms contributing to initiation and progression of esophageal squamous cell carcinoma are still poorly understood. Development of DNA microarray technology allows high-throughput identification of gene expression profiles in cancers. In order to identify molecules as candidates for early diagnosis and/or as therapeutic targets, we analyzed the mRNA expression profiles of 20 cases of ESCC using whole genome DNA microarrays. A total of 2,235 genes were differentially regulated in the tumors as compared to the corresponding adjacent normal epithelium of which 881 were significantly upregulated. We validated two molecules that were not previously reported to be overexpressed in ESCC, oral cancer overexpressed 2 (ORAOV2) and fibroblast activation protein (FAP), by immunohistochemical labeling of tissue microarrays and archival tissue sections and found that they were overexpressed in 98% (116/118) and 68% (79/116) of cases, respectively. By gene enrichment analysis, we identified significant downregulation of several genes in the arachidonic acid metabolic pathway. Overall, using this approach we have identified a number of promising novel candidates that can be validated Further for their potential to serve as biomarkers for ESCC.