Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer.
Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer.
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DOI：
10.1002/pros.20786
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发表时间：
2008-08-01
期刊：
影响因子：
2.8
通讯作者：
Ambs, Stefan
中科院分区：
文献类型：
--
作者：
Prueitt, Robyn L.;Yi, Ming;Hudson, Robert S.;Wallace, Tiffany A.;Howe, Tiffany M.;Yfantis, Harris G.;Lee, Dong. H.;Stephens, Robert M.;Liu, Chang-Gong;Calin, George A.;Croce, Carlo M.;Ambs, Stefan
前列腺癌的神经浸润是前列腺癌局部浸润的主要途径。迄今为止，只有少数研究探讨了前列腺肿瘤与PNI之间的分子差异。为了评估PNI中microRNA和蛋白编码基因的参与，我们使用定制的microRNA微阵列和Affyssin基因芯片在50例PNI和7例无PNI的前列腺癌中测定了它们的全基因组表达。原位杂交和免疫组织化学用于验证候选基因。57个腺癌的无监督分类揭示了具有不同的全局microRNA表达的两个肿瘤簇。一个簇包含所有非PNI肿瘤和PNI肿瘤亚组。微阵列数据的显著性分析产生了与PNI相关的microRNA列表。在错误发现率（FDR）<10%时，19种microRNA在PNI肿瘤中的表达高于非PNI肿瘤。表达差异最大的microRNA是miR-224。原位杂交结果显示，这种microRNA在神经周围癌细胞中表达。蛋白质编码基因的分析鉴定了34个转录本，它们在PNI状态下表达不同（FDR <10%）。这些转录物在PNI肿瘤中下调。其中许多编码金属硫蛋白和蛋白质与线粒体定位和参与细胞代谢。与微阵列数据一致，通过免疫组织化学，神经周围癌细胞倾向于具有比非神经周围癌细胞更低的金属硫蛋白表达。虽然是初步的，但我们的研究结果表明，microRNA表达，线粒体功能和细胞代谢的改变发生在从非侵袭性前列腺肿瘤到PNI肿瘤的过渡阶段。
Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it. To evaluate the involvement of both microRNAs and protein-coding genes in PNI, we determined their genome-wide expression with a custom microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas with PNI and 7 without it. In-situ hybridization and immunohistochemistry was used to validate candidate genes. Unsupervised classification of the 57 adenocarcinomas revealed two clusters of tumors with distinct global microRNA expression. One cluster contained all non-PNI tumors and a subgroup of PNI tumors. Significance analysis of microarray data yielded a list of microRNAs associated with PNI. At a false discovery rate (FDR) < 10%, 19 microRNAs were higher expressed in PNI tumors than in non-PNI tumors. The most differently expressed microRNA was miR-224. In-situ hybridization showed that this microRNA is expressed by perineural cancer cells. The analysis of protein-coding genes identified 34 transcripts that were differently expressed by PNI status (FDR <10%). These transcripts were down-regulated in PNI tumors. Many of those encoded metallothioneins and proteins with mitochondrial localization and involvement in cell metabolism. Consistent with the microarray data, perineural cancer cells tended to have lower metallothionein expression by immunohistochemistry than nonperineural cancer cells. Although preliminary, our findings suggest that alterations in microRNA expression, mitochondrial function, and cell metabolism occur at the transition from a non-invasive prostate tumor to a tumor with PNI.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
4.5
作者：
Montironi, R;Mazzucchelli, R;Mikuz, G
通讯作者：
Mikuz, G
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2.1
作者：
Merrick, GS;Butler, WM;Adamovich, E
通讯作者：
Adamovich, E