Expression profiles of stemness genes in gastrointestinal stromal tumor
Expression profiles of stemness genes in gastrointestinal stromal tumor
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胃肠道间质瘤中干性基因的表达谱
DOI：
10.1016/j.humpath.2018.02.015
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发表时间：
2018-06-01
期刊：
影响因子：
3.3
通讯作者：
Zheng, Jianming
中科院分区：
文献类型：
--
作者：
Bai, Chenguang;Liu, Xiaohong;Zheng, Jianming
胃肠道间质瘤（GIST）被认为起源于肠道Cajal细胞或其干细胞前体，表达干细胞相关标志物，如CD 117、CD 34、DOG 1和巢蛋白。为了进一步表征GIST的表型特征，我们通过分析现有的基因表达谱数据集来检查GIST中一组干性基因的表达谱。我们的研究结果表明，B淋巴瘤莫洛尼鼠白血病病毒插入区1（BMI 1），kruppel样因子4（KLF 4），sal-like蛋白4（SALL 4）和端粒酶逆转录酶（TERT）的mRNA水平在GIST中显著失调。随后，通过免疫组化鉴定GIST标本中BMI 1和TERT的蛋白表达。特别是，我们发现核BMI 1的高表达与GIST中的大肿瘤大小（P = .0239）、高有丝分裂计数（P < .01）、高Ki-67指数（P = .0357）、先进的美国国立卫生研究院（NIH）标准（P = .0025）和先进的世界卫生组织（WHO）分类（P < .01）相关。功能和途径富集分析表明，BMI 1共表达基因大多参与肿瘤生长相关过程，如细胞周期和增殖的调控。此外，我们证实RAS癌基因家族（RAB 18）和肢体发育膜蛋白1（LMBR 1）基因作为GIST细胞中BMI 1的新靶点。这些结果为GIST中干细胞基因的表达谱提供了有价值的信息，并确定核BMI 1是GIST细胞增殖和进展的重要标志物。(C)2018爱思唯尔公司All rights reserved.
Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem cell precursors, and expresses sternness-related markers, such as CD117, CD34, DOG1 and nestin. To further characterize phenotypic features of GISTs, we examined expression profiles of a panel of sternness genes in GISTs, by analyzing existing gene expression profiling datasets. Our results showed that mRNA levels of B-lymphoma moloney murine leukaemia virus insertion region-1 (BMI1), kruppel-like factor 4 (KLF4), sal-like protein 4 (SALL4) and telomerase reverse transcriptase (TERT) were significantly unregulated in GISTs. Subsequently, protein expression of BMI1 and TERT was identified in GIST specimens by immunohistochemistry. Especially, we found that high expression of nuclear BMI1 was associated with large tumor size (P = .0239), high mitotic count (P < .01), high Ki-67 index (P = .0357), advanced National Institute of Health (NIH) criteria (P = .0025) and advanced World Health Organization (WHO) classification (P < .01) in GISTs. Functional and pathway enrichment analysis showed that most of BMI1's coexpressed genes were involved in tumor growth-related process, such as regulation of cell cycle and proliferation. Furthermore, we confirmed RAS oncogene family (RAB18) and limb development membrane protein 1 (LMBR1) genes as novel targets for BMI1 in GIST cells. These results provide valuable information for the expression profiles of sternness genes in GISTs, and identified nuclear BMI1 as an important marker of GIST cell proliferation and progression. (C) 2018 Elsevier Inc. All rights reserved.