Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer.
Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer.
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DOI：
10.1053/j.gastro.2010.04.008
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发表时间：
2010-07
期刊：
影响因子：
29.4
通讯作者：
Goldenring JR
中科院分区：
文献类型：
--
作者：
Lee HJ;Nam KT;Park HS;Kim MA;Lafleur BJ;Aburatani H;Yang HK;Kim WH;Goldenring JR
肠化生（IM）和表达痉挛解多肽的化生（SPEM）是胃癌发生的前体。我们试图通过患者化生病变的基因表达谱来鉴定胃化生和胃癌的分子生物标志物。采用激光捕获显微解剖技术对患者标本中分离的IM和SPEM细胞进行cDNA芯片分析。通过IM、SPEM和胃癌组织的免疫染色分析，证实了化生病变中转录物的上调。在胃癌患者样本的测试集（n=450）和验证集（n=502）中，分析了在胃癌组织中特异性高表达的蛋白质与生存率的关系。与正常主细胞相比，IM或SPEM样品中有858个基因差异表达。对12个蛋白进行免疫染色检测，其中IM新标记3个（ACE2、LGALS4、AKR1B10）， SPEM新标记3个（OLFM4、LYZ、DPCR1）。在IM或SPEM中表达的13个蛋白中，有8个蛋白在17%-50%的人胃癌组织中表达（MUC13、OLFM4、CDH17、KRT20、MUC5AC、LGALS4、AKR1B10、REG4）。在试验和验证集中，CDH17或MUC13的表达与患者生存相关。多因素分析显示，CDH17是I期或淋巴结阴性患者的独立预后因素。我们利用人类化生病变的基因表达谱确定了几种新的IM、SPEM和胃癌的生物标志物。胃癌组织中CDH17和MUC13表达上调。CDH17是一种很有希望的早期胃癌预后标志物。
Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. cDNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplstic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n=450) and a validation set (n=502) of samples from gastric cancer patients. Compared to normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%–50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and a validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was upregulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early-stage gastric cancer.
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影响因子：
7.3
作者：
Oue, N;Mitani, Y;Yasui, W
通讯作者：
Yasui, W
影响因子：
7.3
作者：
Ko, S;Chu, KM;Wong, J
通讯作者：
Wong, J
影响因子：
29.4
作者：
Nozaki, Koji;Ogawa, Masako;Goldenring, James R.
通讯作者：
Goldenring, James R.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
24.5
作者：
Grötzinger, C;Kneifel, J;Gessner, R
通讯作者：
Gessner, R