Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.
Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.
复制标题
DOI：
10.1371/journal.pone.0174778
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Connor JR
中科院分区：
文献类型：
--
作者：
Lee SY;Zhu J;Salzberg AC;Zhang B;Liu DJ;Muscat JE;Langan ST;Connor JR
人血色病蛋白（HFE）参与铁代谢。两种主要的HFE多态性H63 D和C282 Y与癌症风险增加相关。以前，我们报道了基于H63 D或C282 Y HFE多态性的多形性胶质母细胞瘤（GBM）患者的总生存率的性别效应降低。然而，HFE基因中其他单核苷酸变异（SNV）对癌症发生和进展的影响尚未得到系统研究。为了在更大的样本中扩展我们的发现，并鉴定其他HFE SNV，我们使用癌症基因组图谱（TCGA）GBM（仅限高加索人）数据库分析了HFE基因中体细胞SNV的频率及其与GBM患者生存期的关系。与1000个基因组相比，我们在TCGA GBM患者的血液正常人中发现了9个频率增加的SNV。在9个SNV中，7个SNV位于内含子中，2个SNV（即，H63D，C282Y）。统计学分析表明，TCGA GBM的血液正常样本比1000 Genome具有更多的H63 D（p = 0.0002，95%CI：0.2119-0.3223）或C282 Y（p = 0.0129，95%CI：0.0474-0.1159）HFE多态性。264个GBM样品的Kaplan-Meier存活曲线显示野生型（WT）HFE和H63 D之间以及WT HFE和C282 Y GBM患者之间没有差异。此外，基于HFE基因型的男性/女性GBM患者的生存率没有差异。HFE表达与生存率无相关性。总之，目前的结果表明，体细胞HFE多态性不影响GBM的TCGA数据集GBM患者的生存。
Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119–0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474–0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients’ survival in the TCGA data set of GBM.