ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.
ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.
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ANKS1B是透明细胞肾细胞癌中与吸烟相关的分子改变。
DOI：
10.1186/1471-2490-14-14
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发表时间：
2014-01-31
期刊：
影响因子：
2
通讯作者：
Parker AS
中科院分区：
文献类型：
--
作者：
Eckel-Passow JE;Serie DJ;Bot BM;Joseph RW;Cheville JC;Parker AS
吸烟与透明细胞肾细胞癌（ccRCC）风险增加之间的关联已经建立;然而，关于这种关联的分子机制的数据有限。我们使用多阶段设计来鉴定和验证与吸烟相关的ccRCC相关的基因。我们首先进行了一项微阵列研究，以比较有吸烟史（n = 23）和无吸烟史（n = 42）患者之间患者匹配的ccRCC和正常肾组织中的基因表达模式。分析首先根据肥胖状态（ccRCC的另一个主要风险因素）进行分层，然后合并并一起分析。为了鉴定其中吸烟者相对于非吸烟者的倍数变化在肿瘤组织中与患者匹配的正常肾组织相比不同的基因，我们鉴定了具有显著的组织类型-吸烟状态相互作用p值的Affyphin探针组。然后，我们在28名吸烟者和54名非吸烟者的独立样本中对前8个候选基因进行了RT-PCR验证。我们确定了15个探针集，这些探针集映射到与吸烟相关的ccRCC有候选关联的8个基因：ANKS 1B，ACOT 6，PPWD 1，EYS，LIMCH 1，CHRNA 6，MT 1G和ZNF 600。使用RT-PCR，我们验证了ANKS 1B的表达在吸烟相关的ccRCC中优先下调。我们提供了第一个证据表明，相对于吸烟者患者匹配的正常肾组织，在ccRCC肿瘤中ANKS 1B表达下调。因此，ANKS 1B应进一步探索作为早期检测和预防吸烟者ccRCC的新途径。
An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC. We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between patients with (n = 23) and without (n = 42) a history of smoking. Analyses were first stratified on obesity status (the other primary risk factor for ccRCC) and then combined and analyzed together. To identify genes where the fold change in smokers relative to non-smokers was different in tumor tissues in comparison to patient-matched normal kidney tissues, we identified Affymetrix probesets that had a significant tissue type-by-smoking status interaction pvalue. We then performed RT-PCR validation on the top eight candidate genes in an independent sample of 28 smokers and 54 non-smokers. We identified 15 probesets that mapped to eight genes that had candidate associations with smoking-related ccRCC: ANKS1B, ACOT6, PPWD1, EYS, LIMCH1, CHRNA6, MT1G, and ZNF600. Using RT-PCR, we validated that expression of ANKS1B is preferentially down-regulated in smoking-related ccRCC. We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. Thus, ANKS1B should be explored further as a novel avenue for early detection as well as prevention of ccRCC in smokers.
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影响因子：
4.7
作者：
Eckel-Passow, Jeanette E.;Serie, Daniel J.;Parker, Alexander S.
通讯作者：
Parker, Alexander S.
影响因子：
6.4
作者：
Hunt, JD;van der Hel, OL;Brennan, P
通讯作者：
Brennan, P
影响因子：
2.1
作者：
McCall, Matthew N.;Bolstad, Benjamin M.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.
影响因子：
64.8
作者：
Evan, GI;Vousden, KH
通讯作者：
Vousden, KH
影响因子：
4.7
作者：
Lin, Jie;Lu, Charles;Wu, Xifeng
通讯作者：
Wu, Xifeng