MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.
MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.
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DOI：
10.1186/s12863-016-0348-7
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发表时间：
2016-02-13
期刊：
影响因子：
2.9
通讯作者：
Shete S
中科院分区：
文献类型：
--
作者：
Reyes-Gibby CC;Wang J;Silvas MR;Yu R;Yeung SC;Shete S
遗传易感性在癌症患者发生疼痛的风险中起着重要作用。作为一种复杂的性状，多重基因是这种易感性的基础。我们使用基因网络分析来确定新诊断为头颈部鳞状细胞癌（HNSCC）患者疼痛相关的新靶基因。我们首先根据文献检索从36篇出版物中鉴定出36个与癌症疼痛相关的基因（即焦点基因）。匠心途径分析（Ingenuity Pathway Analysis， IPA）通过途径关系鉴定出与36个重点基因在功能上相关的其他基因，共产生82个基因。随后，在Illumina HumanOmniExpress-12v1平台上，从82个ipa选择的基因中选择了800个snp。800个候选snp（涵盖82个基因）与1368例HNSCC患者（206例重度疼痛患者对1162例非重度疼痛患者）疼痛的关联分析显示，MAPK1/ERK2是MAP激酶家族的一个基因（rs8136867， p值= 8.92 × 10−4；比值比[OR] = 1.33, 95%可信区间[CI]: 1.13-1.58）具有最高的显著性。其他顶级基因PIK3C2G (PI3K(复杂)的一员,rs10770367, p值= 1.10×10−3;或= 1.46,95%置信区间CI: 1.16 - -1.82), TCRA (t细胞受体的α链rs6572493 p值= 2.84×10−3;或= 0.70,95%置信区间CI: 0.55 - -0.88), PDGFC(血小板源生长因子C, rs6845322, p值= 4.88×10−3;或= 1.32,95%置信区间CI: 1.09 - -1.60),和CD247 (CD3成员rs2995082 p值= 7.79×10−3;或= 0.76,95% CI: 0.62—-0.93)。我们的发现为癌症患者疼痛提供了新的候选基因和生物学途径。对这些候选基因变异的进一步研究可以为治疗癌痛的临床决策提供信息。本文的在线版本（doi:10.1186/s12863-016-0348-7）包含补充材料，可供授权用户使用。
Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The Ingenuity Pathway Analysis (IPA) analysis identified additional genes that are functionally related to the 36 focus genes through pathway relationships yielding a total of 82 genes. Subsequently, 800 SNPs within the 82 IPA-selected genes on the Illumina HumanOmniExpress-12v1 platform were selected from a large-scale genotyping effort. Association analyses between the 800 candidate SNPs (covering 82 genes) and pain in a patient cohort of 1368 patients with HNSCC (206 patients with severe pain vs. 1162 with non-severe pain) showed the highest significance for MAPK1/ERK2, a gene belonging to the MAP kinase family (rs8136867, p value = 8.92 × 10−4; odds ratio [OR] = 1.33, 95 % confidence interval [CI]: 1.13–1.58). Other top genes were PIK3C2G (a member of PI3K [complex], rs10770367, p value = 1.10 × 10−3; OR = 1.46, 95 % CI: 1.16–1.82), TCRA (the alpha chain of T-cell receptor, rs6572493, p value = 2.84 × 10−3; OR = 0.70, 95 % CI: 0.55–0.88), PDGFC (platelet-derived growth factor C, rs6845322, p value = 4.88 × 10−3; OR = 1.32, 95 % CI: 1.09–1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 × 10−3; OR = 0.76, 95 % CI: 0.62–0.93). Our findings provide novel candidate genes and biological pathways underlying pain in cancer patients. Further study of the variations of these candidate genes could inform clinical decision making when treating cancer pain. The online version of this article (doi:10.1186/s12863-016-0348-7) contains supplementary material, which is available to authorized users.