Identification of marker genes and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas
Identification of marker genes and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas
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DOI：
10.1007/s00535-018-1489-4
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发表时间：
2019-02-01
影响因子：
6.3
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
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作者：
Sakaguchi, Yoshiki;Yamamichi, Nobutake;Koike, Kazuhiko
背景这些肿瘤的发病机制和癌变机制尚不完全清楚。本研究的目的是通过基因表达分析，以确定癌前十二指肠腺瘤和早期腺癌的特异性遗传标记和途径。MethodsGene expression profiling在4对十二指肠腺瘤/腺癌和相应的匹配正常组织进行。在7个独立对中鉴定并确认了具有一致表达差异的基因。结果626个探针在十二指肠腺瘤/腺癌组织中的表达差异均在2倍以上。对肿瘤和正常粘膜之间表达差异最显著的基因（KLK 7、KLK 6、CEMIP、MMP 7、KRT 17、LGR 5、G6 PC、S100 G、APOA 1）进行逆转录聚合酶链反应，验证了基因表达分析的结果。GSEA显示十二指肠腺瘤/腺癌与结直肠腺瘤之间存在强相关性（p
BackgroundThe mechanism behind the pathogenesis and carcinogenesis of these neoplasms is not fully understood. The objective of this study was to identify genetic markers and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas through gene expression analysis.MethodsGene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. Genes with consistent expression differences were identified and confirmed in 7 independent pairs. Gene set enrichment analysis (GSEA) was performed to characterize gene expression profiles of duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of candidate oncogenic genes.Results626 probes consistently demonstrated over a twofold expression difference between tumor-normal pairs. Reverse transcriptase polymerase chain reaction of genes with the most prominent difference in expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17, LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p