Gene expression profile of gastric carcinoma: Identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression
Gene expression profile of gastric carcinoma: Identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression
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DOI：
10.1158/0008-5472.can-03-3514
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发表时间：
2004-04-01
期刊：
影响因子：
11.2
通讯作者：
Yasui, W
中科院分区：
文献类型：
--
作者：
Oue, N;Hamai, Y;Yasui, W
胃癌（GC）是全世界最常见的恶性肿瘤之一。为了更好地了解这种疾病的遗传基础，我们对四个原发性 GC 样本和一个相关的淋巴结转移样本进行了基因表达系列分析 (SAGE)。我们总共获得了 137,706 个表达标签（Gene Expression Omnibus 登录号 GSE 545，SAGE Hiroshima 胃癌组织），其中 38,903 个是独特的。比较我们的GC文库中包含不同阶段和不同组织学的标签，我们发现了一些可能参与侵袭、转移和癌变的基因和标签。其中，我们选择了 27 个基因，并通过定量逆转录 PCR 测量了另外 46 个 GC 样本中的 mRNA 表达水平。经常过度表达的基因（肿瘤/正常比率> 2）是COL1A1（过度表达病例的百分比，78.3％），CDH17（73.9％），APOC1（67.4％），COL1A2（58.7％），YF13H12（52.2％），CEACAM6（50.0％），APOE（50.0％），REGIV (47.8%), S100A11 (41.3%) 和 FUS (41.3%)。其中，CDH17和APOE mRNA表达水平与肿瘤侵袭深度相关（分别为P=0.0060和P=0.0139），FUS和APOE mRNA表达水平与淋巴结转移程度相关（分别为P=0.0416和P=0.0006）。此外，FUS、COL1A1、COL1A2 和 APOE 的 mRNA 表达水平与分期相关（分别为 P = 0.0414、P = 0.0156、P = 0.0395 和 P = 0.0125）。定量逆转录 PCR 分析还显示，46 个 GC 样本中有 14 个 (30.4%) 具有高水平的 REGIV 表达（> 100 个任意单位），但在非癌组织中则没有。我们通过蛋白质印迹法在转染 pcDNA-RegIV-V5 的细胞的培养基中检测到 V5 标记的 RegIV 蛋白。我们的结果提供了可能参与GC侵袭、转移和癌变的候选基因列表。 REGIV 可作为 GC 的特异性生物标志物。
Gastric carcinoma (GC) is one of the most common malignancies worldwide. To better understand the genetic basis of this disease, we performed serial analysis of gene expression (SAGE) on four primary GC samples and one associated lymph node metastasis. We obtained a total of 137,706 expressed tags (Gene Expression Omnibus accession number GSE 545, SAGE Hiroshima gastric cancer tissue), including 38,903 that were unique. Comparing tags from our GC libraries containing different stages and different histologies, we found several genes and tags that are potentially involved in invasion, metastasis, and carcinogenesis. Among these, we selected 27 genes and measured mRNA expression levels in an additional 46 GC samples by quantitative reverse transcription-PCR. Frequently overexpressed genes (tumor/normal ratio > 2) were COL1A1 (percentage of cases with overexpression, 78.3%), CDH17 (73.9%), APOC1 (67.4%), COL1A2 (58.7%), YF13H12 (52.2%), CEACAM6 (50.0%), APOE (50.0%), REGIV (47.8%), S100A11 (41.3%), and FUS (41.3%). Among these genes, mRNA expression levels of CDH17 and APOE were associated with depth of tumor invasion (P = 0.0060 and P = 0.0139, respectively), and those of FUS and APOE were associated with degree of lymph node metastasis (P = 0.0416 and P = 0.0006, respectively). In addition, mRNA expression levels of FUS, COL1A1, COL1A2, and APOE were associated with stage (P = 0.0414, P = 0.0156, P = 0.0395, and P = 0.0125, respectively). Quantitative reverse transcription-PCR analysis also showed a high level of REGIV expression (> 100 arbitrary units) in 14 of 46 GC samples (30.4%) but not in noncancerous tissues. We detected V5-tagged RegIV protein in the culture media of cells transfected with pcDNA-RegIV-V5 by Western blot. Our results provide a list of candidate genes that are potentially involved in invasion, metastasis, and carcinogenesis of GC. REGIV may serve as a specific biomarker for GC.