Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan,
Ann Surg Oncol. 2013 Dec;20 Suppl 3:S324-35. doi: 10.1245/s10434-012-2418-z. Epub 2012 May 30.
The importance of mesenchymal characteristics has not been fully elucidated in esophageal cancer.
Ten normal and 77 tumor specimens were collected. Microarray analysis was performed to analyze the expression patterns of epithelial markers, mesenchymal markers, epithelial mesenchymal transition (EMT)-related genes and stem cell markers. RT-PCR analysis was conducted to confirm the results of microarray analysis. Immunohistochemical analysis was performed to verify the level of protein expression. Statistical analysis was performed to investigate the correlation between selected genes and clinicopathological factors.
Microarray analysis showed that epithelial markers were significantly down-regulated whereas mesenchymal markers and EMT transcription factors were up-regulated in cancer cells. Two types of gene expression patterns were found in the clustering analysis, type 1 tumors and type 2 tumors. Type 1 tumor clusters did not reveal a fixed gene expression pattern whereas type 2 tumor clusters revealed up-regulation of mesenchymal markers EMT inducers and related genes. Vimentin and fibronectin were selected to distinguish between tumor types 1 and 2. Type 2 tumors showed significantly larger tumor sizes (p < 0.0001), wider ranges of lymph node metastasis (p = 0.0057), and a more severe clinical stage (p < 0.0001) than did type 1 tumors. The prognosis of patients with type 2 tumors was significantly worse than that of patients with type 1 tumors. Univariate and multivariate analyses revealed that classification of type 2 tumors was an independent prognostic factor.
The analysis of mesenchymal markers in esophageal cancer is useful in distinguishing patients with a poor prognosis.
间充质特征在食管癌中的重要性尚未完全阐明。
收集了 10 份正常和 77 份肿瘤标本。进行微阵列分析以分析上皮标志物、间充质标志物、上皮间质转化（EMT）相关基因和干细胞标志物的表达模式。进行 RT-PCR 分析以验证微阵列分析的结果。进行免疫组织化学分析以验证蛋白表达水平。进行统计分析以研究选定基因与临床病理因素之间的相关性。
微阵列分析显示，癌细胞中上皮标志物显著下调，而间充质标志物和 EMT 转录因子上调。聚类分析发现两种类型的基因表达模式，即 1 型肿瘤和 2 型肿瘤。1 型肿瘤簇没有显示固定的基因表达模式，而 2 型肿瘤簇显示间充质标志物 EMT 诱导物和相关基因的上调。选择波形蛋白和纤连蛋白来区分肿瘤类型 1 和 2。2 型肿瘤的肿瘤大小明显更大（p < 0.0001），淋巴结转移范围更广（p = 0.0057），临床分期更严重（p < 0.0001），与 1 型肿瘤相比。2 型肿瘤患者的预后明显差于 1 型肿瘤患者。单因素和多因素分析表明，2 型肿瘤的分类是独立的预后因素。
对食管癌中间充质标志物的分析有助于区分预后不良的患者。
