Associations of two-pore domain potassium channels and triple negative breast cancer subtype in The Cancer Genome Atlas: systematic evaluation of gene expression and methylation.
Associations of two-pore domain potassium channels and triple negative breast cancer subtype in The Cancer Genome Atlas: systematic evaluation of gene expression and methylation.
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DOI：
10.1186/s13104-017-2777-4
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发表时间：
2017-09-12
影响因子：
1.8
通讯作者：
Argos M
中科院分区：
文献类型：
--
作者：
Dookeran KA;Zhang W;Stayner L;Argos M
目前尚不清楚2孔结构域钾通道是否是与生物学侵袭性三阴性型乳腺肿瘤相关的具有差异表达的新型分子标记物。我们的目的是系统地评估癌症基因组图谱侵袭性乳腺癌数据集中2孔结构域钾通道基因表达和DNA甲基化与三阴性亚型的相关性。对1040名女性的所有15个2孔结构域钾家族基因的甲基化和表达数据进行了检查，并使用年龄/种族调整的广义线性模型和Bonferroni校正的显著性阈值评估了与三阴性亚型（vs. Luminal A）的相关性。使用斯皮尔曼相关性评估亚型相关CpG基因座与表达相关的功能。KCNK 5、KCNK 9和KCNK 12的过表达以及KCNK 6和KCNK 15的低表达与三阴性亚型显著相关（Bonferroni校正p < 0.0033）。共有195个（114个低甲基化和81个高甲基化）CpG位点与三阴性亚型显著相关（Bonferroni校正p < 8.22 × 10−8）。在三阴性与管腔A亚型中差异观察到的显著负相关的表达模式被证明为：KCNK 2（基因体：cg 04923840，cg 13916421），KCNK 5（基因体：cg 05255811、cg 18705155、cg 09130674、cg 21388745、cg 00859574）和KCNK 9（TSS 1500：cg 21415530，cg 12175729; KCNK 9/TRAPPC 9基因间区：cg 17336929，cg 25900813，cg 03919980）。KCNK 5和KCNK 9列出的CpG基因座均显示三阴性与管腔A亚型的概率相对低甲基化。三阴性亚型与不同的2孔结构域钾通道表达模式相关。KCNK 5和KCNK 9过表达似乎与CpG位点低甲基化功能相关。本文的在线版本（doi：10.1186/s13104-017-2777-4）包含补充材料，可供授权用户使用。
It is unclear whether 2-pore domain potassium channels are novel molecular markers with differential expression related to biologically aggressive triple-negative type breast tumors. Our objective was to systematically evaluate associations of 2-pore domain potassium channel gene expression and DNA methylation with triple-negative subtype in The Cancer Genome Atlas invasive breast cancer dataset. Methylation and expression data for all fifteen 2-pore domain potassium family genes were examined for 1040 women, and associations with triple-negative subtype (vs. luminal A) were evaluated using age/race adjusted generalized-linear models, with Bonferroni-corrected significance thresholds. Subtype associated CpG loci were evaluated for functionality related to expression using Spearman’s correlation. Overexpression of KCNK5, KCNK9 and KCNK12, and underexpression of KCNK6 and KCNK15, were significantly associated with triple-negative subtype (Bonferroni-corrected p < 0.0033). A total of 195 (114 hypomethylated and 81 hypermethylated) CpG loci were found to be significantly associated with triple-negative subtype (Bonferroni-corrected p < 8.22 × 10−8). Significantly negatively correlated expression patterns that were differentially observed in triple-negative vs. luminal A subtype were demonstrated for: KCNK2 (gene body: cg04923840, cg13916421), KCNK5 (gene body: cg05255811, cg18705155, cg09130674, cg21388745, cg00859574) and KCNK9 (TSS1500: cg21415530, cg12175729; KCNK9/TRAPPC9 intergenic region: cg17336929, cg25900813, cg03919980). CpG loci listed for KCNK5 and KCNK9 all showed relative hypomethylation for probability of triple-negative vs. luminal A subtype. Triple-negative subtype was associated with distinct 2-pore domain potassium channel expression patterns. Both KCNK5 and KCNK9 overexpression appeared to be functionally related to CpG loci hypomethylation. The online version of this article (doi:10.1186/s13104-017-2777-4) contains supplementary material, which is available to authorized users.