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应用存档福尔马林固定石蜡包埋组织进行人肝母细胞瘤的基因表达谱分析。

Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues.

机构信息

Department of Pathology, Seoul National University College of Medicine, #28 Yongon-dong, Jongro-gu, Seoul, 110-799, South Korea.

出版信息

Virchows Arch. 2011 Apr;458(4):453-65. doi: 10.1007/s00428-011-1043-8. Epub 2011 Mar 3.

Abstract

We elucidated the genetic profile of hepatoblastomas (HBLs) to identify diagnostic and prognostic markers. RNA was extracted from 32 formalin-fixed, paraffin-embedded HBLs and corresponding nonneoplastic liver (NNL) tissues, and cDNA-mediated annealing, selection, extension, and ligation (DASL) chip assays were performed. Immunohistochemistry was performed to confirm the expression of Yin Yang 1 (YY1) protein in HBL. Twenty-four genes that were associated with signal transduction, cell-cell adhesion, cell cycle regulation, and apoptosis were differentially expressed in HBL and NNL tissues. Two apoptosis-associated genes, MYCN and BIRC5, were highly upregulated in HBL. Eight genes, including YY1 and IGF1, were upregulated in HBL cases that had a poor prognosis. Thirty-eight genes, including YY1, were differentially expressed according to histologic differentiation of HBL, and the immunohistochemical expression of YY1 was correlated with poor HBL differentiation. Thus, using DASL chip assays, we report the gene expression profiles of HBL, which suggest new candidate prognostic and diagnostic genetic markers and putative therapeutic targets for HBL.

摘要

我们阐明了肝母细胞瘤(HBL)的遗传特征,以确定诊断和预后标志物。从 32 例福尔马林固定、石蜡包埋的 HBL 和相应的非肿瘤性肝(NNL)组织中提取 RNA,并进行 cDNA 介导的退火、选择、延伸和连接(DASL)芯片分析。进行免疫组织化学染色以确认 HBL 中 Yin Yang 1(YY1)蛋白的表达。在 HBL 和 NNL 组织中,有 24 个与信号转导、细胞-细胞黏附、细胞周期调控和细胞凋亡相关的基因表达存在差异。两个与细胞凋亡相关的基因,MYCN 和 BIRC5,在 HBL 中高度上调。有 8 个基因,包括 YY1 和 IGF1,在预后不良的 HBL 病例中上调。包括 YY1 在内的 38 个基因根据 HBL 的组织学分化而表达不同,YY1 的免疫组织化学表达与 HBL 的低分化相关。因此,我们通过 DASL 芯片分析报告了 HBL 的基因表达谱,这提示了新的候选预后和诊断遗传标志物以及 HBL 的潜在治疗靶点。

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