Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data.
Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data.
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DOI：
10.3892/or.2015.3993
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发表时间：
2015-07
期刊：
影响因子：
4.2
通讯作者：
Jamal R
中科院分区：
文献类型：
--
作者：
Kok-Sin T;Mokhtar NM;Ali Hassan NZ;Sagap I;Mohamed Rose I;Harun R;Jamal R
除遗传突变外，表观遗传学改变是一种有助于结直肠癌的肿瘤转化的常见现象。来自类似的结直肠组织样品的表观基因组和转录组数据。在55个成对的癌症和邻近的正常上皮细胞上，无甲基甲基化27个珠子使用150个sT阵列进行了甲基化验证，将55个配对组织中的15个用于基因表达。依赖性探针放大（MS-MLPA）技术。根据≥2倍的变化和假发现率（FDR）p值<0.05，我们发现了两个分析的癌症和正常样品之间的良好分离。 CPG位点也发现了709个上调的基因表达分析的基因。 27个重叠的基因被下调的表达和4个高甲基化的基因，其中一个基因被发现是甲基化的，并且被鉴定出最丰富的分子途径。在本研究中，我们成功鉴定了一组显示甲基化和基因的基因具有高纯度的彩色癌组织的表达变化。
Apart from genetic mutations, epigenetic alteration is a common phenomenon that contributes to neoplastic transformation in colorectal cancer. Transcriptional silencing of tumor-suppressor genes without changes in the DNA sequence is explained by the existence of promoter hypermethylation. To test this hypothesis, we integrated the epigenome and transcriptome data from a similar set of colorectal tissue samples. Methylation profiling was performed using the Illumina InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal epithelial cells. Fifteen of the 55 paired tissues were used for gene expression profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was carried out on 150 colorectal tissues using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised hierarchical clustering in the two microarray datasets showed good separation between cancer and normal samples. Significant genes from the two analyses were obtained based on a ≥2-fold change and a false discovery rate (FDR) P-value of <0.05. We identified 1,081 differentially hypermethylated CpG sites and 36 hypomethylated CpG sites. We also found 709 upregulated and 699 downregulated genes from the gene expression profiling. A comparison of the two datasets revealed 32 overlapping genes with 27 being hypermethylated with downregulated expression and 4 hypermethylated with upregulated expression. One gene was found to be hypomethylated and downregulated. The most enriched molecular pathway identified was cell adhesion molecules that involved 4 overlapped genes, JAM2, NCAM1, ITGA8 and CNTN1. In the present study, we successfully identified a group of genes that showed methylation and gene expression changes in well-defined colorectal cancer tissues with high purity. The integrated analysis gives additional insight regarding the regulation of colorectal cancer-associated genes and their underlying mechanisms that contribute to colorectal carcinogenesis.
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影响因子：
3.8
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
通讯作者：
Soong R
影响因子：
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影响因子：
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作者：
Flamen, P;Hoekstra, OS;Mortelmans, L
通讯作者：
Mortelmans, L