Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort.
Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort.
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DOI：
10.1186/bcr3428
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发表时间：
2013-05-24
期刊：
影响因子：
--
通讯作者：
Taylor JA
中科院分区：
文献类型：
--
作者：
Godfrey AC;Xu Z;Weinberg CR;Getts RC;Wade PA;DeRoo LA;Sandler DP;Taylor JA
microRNA（miRNAs）是一种长度在18-22个核苷酸之间的非编码单链小RNA，可调节基因表达。与正常组织相比，肿瘤中miRNA的表达发生了变化;有证据表明，与健康个体相比，这些变化可能反映在癌症病例的血清中。这还有待于在诊断前收集样本的前瞻性研究中进行检查。我们使用Affyellow阵列检测了姐妹研究中410名参与者的血清miRNA表达谱，这是一项包含50，884名女性的前瞻性队列研究。队列中的所有女性在入组时从未被诊断出患有乳腺癌。我们比较了205名随后患乳腺癌的女性和205名未患乳腺癌的女性的总体miRNA表达模式。此外，在病例组中，我们研究了血清中miRNA表达与不同肿瘤特征的相关性，包括激素状态（ER，PR和HER-2）和淋巴结状态。总体而言，芯片上的1，105种人类miRNAs中有414种在50名或更多女性中表达高于背景水平。当使用条件logistic回归将对照组与病例组的平均表达进行比较时，发现21种miRNA差异表达（P≤.05）。使用qRT-PCR对5例病例和5例对照的小的独立样本进行检测，我们证实了病例中3种最高表达的miRNA，miR-18 a，miR-181 a和miR-222的过表达;在这个小的集合中差异没有统计学意义。已知21种差异表达的miRNA靶向至少82个基因;使用基因列表进行通路分析，我们发现参与癌症相关过程的基因富集。在仅限于21种miRNAs的单独病例-病例分析中，我们发现7种miRNAs在HER-2表达不同的乳腺肿瘤妇女中具有差异表达，10种miRNAs在淋巴结状态下具有差异表达。血清中的miRNA水平显示了后来患癌症的女性与那些保持无癌的女性之间的一些小差异。
MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis. We used Affymetrix arrays to examine serum miRNA expression profiles in 410 participants in the Sister Study, a prospective cohort study of 50,884 women. All women in the cohort had never been diagnosed with breast cancer at the time of enrollment. We compared global miRNA expression patterns in 205 women who subsequently developed breast cancer and 205 women who remained breast cancer-free. In addition within the case group we examined the association of miRNA expression in serum with different tumor characteristics, including hormone status (ER, PR, and HER-2) and lymph node status. Overall, 414 of 1,105 of the human miRNAs on the chip were expressed above background levels in 50 or more women. When the average expression among controls was compared to cases using conditional logistic regression, 21 miRNAs were found to be differentially expressed (P≤.05). Using qRT-PCR on a small, independent sample of 5 cases and 5 controls we verified overexpression of the 3 highest expressing miRNAs among cases, miR-18a, miR-181a, and miR-222; the differences were not statistically significant in this small set. The 21 differentially expressed miRNAs are known to target at least 82 genes; using the gene list for pathway analysis we found enrichment of genes involved in cancer-related processes. In a separate case-case analyses restricted to the 21 miRNAs, we found 7 miRNAs with differential expression for women whose breast tumors differed by HER-2 expression, and 10 miRNAs with differential expression by nodal status. miRNA levels in serum show a number of small differences between women who later develop cancer versus those who remain cancer-free.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1073/pnas.96.24.14037
发表时间：
1999-11-23
影响因子：
11.1
作者：
Cmarik, JL;Min, HZ;Colburn, NH
通讯作者：
Colburn, NH
影响因子：
4
作者：
Heneghan, Helen M.;Miller, Nicola;Kerin, Michael J.
通讯作者：
Kerin, Michael J.
影响因子：
3.7
作者：
Hunter, Melissa Piper;Ismail, Noura;Zhang, Xiaoli;Aguda, Baltazar D.;Lee, Eun Joo;Yu, Lianbo;Xiao, Tao;Schafer, Jeffrey;Lee, Mei-Ling Ting;Schmittgen, Thomas D.;Nana-Sinkam, S. Patrick;Jarjoura, David;Marsh, Clay B.
通讯作者：
Marsh, Clay B.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM