Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer
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DOI：
10.3390/cancers11081142
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发表时间：
2019-08-01
期刊：
影响因子：
5.2
通讯作者：
Grade, Marian
中科院分区：
文献类型：
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作者：
Flebbe, Hannah;Hamdan, Feda H.;Grade, Marian
表观遗传学改变在癌症的发展和进展中起着核心作用。组蛋白3在赖氨酸27处的乙酰化（H3 K27 ac）特异性地标记活性基因。虽然染色质免疫沉淀（ChIP）和下一代测序（ChIP-seq）分析通常在细胞系中进行，但原发性肿瘤的数据有限。因此，我们研究了是否可以在原发性直肠癌中识别H3 K27 ac占用的癌症特异性改变。获得来自原发性直肠癌和匹配粘膜的组织样品。进行H3 K27 ac的ChIP-seq，并鉴定差异占据的区域。在来自独立患者队列的基因表达数据中检查了在肿瘤和粘膜之间显示差异占据的所选基因的表达。通过免疫组织化学进一步检查四种蛋白质的差异表达。在原发性直肠癌和匹配的粘膜中成功地进行了H3 K27 ac的ChIP-seq，并在44个区域上显示了差异结合。这导致鉴定出具有增加的H3 K27 ac的基因，即，RIPK 2、FOXQ 1、KRT 23和EPHX 4在独立数据集中也在原发性直肠癌中高度上调。这四种蛋白的表达增加通过免疫组织化学证实。这项研究证明了基于ChIP-seq的原发性直肠癌表观基因组定位的可行性，并证实了H3 K27 ac占有率预测基因表达差异的价值。
Epigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell lines, only limited data are available from primary tumors. We therefore examined whether cancer-specific alterations in H3K27ac occupancy can be identified in primary rectal cancer. Tissue samples from primary rectal cancer and matched mucosa were obtained. ChIP-seq for H3K27ac was performed and differentially occupied regions were identified. The expression of selected genes displaying differential occupancy between tumor and mucosa were examined in gene expression data from an independent patient cohort. Differential expression of four proteins was further examined by immunohistochemistry. ChIP-seq for H3K27ac in primary rectal cancer and matched mucosa was successfully performed and revealed differential binding on 44 regions. This led to the identification of genes with increased H3K27ac, i.e., RIPK2, FOXQ1, KRT23, and EPHX4, which were also highly upregulated in primary rectal cancer in an independent dataset. The increased expression of these four proteins was confirmed by immunohistochemistry. This study demonstrates the feasibility of ChIP-seq-based epigenome mapping of primary rectal cancer and confirms the value of H3K27ac occupancy to predict gene expression differences.