Two-dimensional transcriptome profiling: Identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens
Two-dimensional transcriptome profiling: Identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens
复制标题
DOI：
10.1158/0008-5472.can-05-4264
复制
发表时间：
2006-04-15
期刊：
影响因子：
11.2
通讯作者：
Fan, JB
中科院分区：
文献类型：
--
作者：
Li, HR;Wang-Rodriguez, J;Fan, JB
特定mRNA亚型的表达可以独特地反映细胞的生物学状态，因为它反映了转录和转录后调节的综合结果。在这项研究中，我们构建了一个剪接阵列，以检查来自先前与前列腺癌有关的一组基因的1,500种mRNA亚型，并鉴定了大量细胞类型特异性mRNA亚型。我们还开发了一种新的“二维”分析策略，同时量化剪接和转录丰度的变化;结果显示前列腺癌细胞中转录和剪接之间存在广泛的共变。利用我们的技术分析来自福尔马林固定的石蜡包埋组织的RNA的能力，我们使用独立的组织样本组进行特征选择和交叉分析，推导出一组特定的前列腺癌mRNA亚型生物标志物。通过激光捕获显微切割进一步验证了许多癌症特异性剪接开关事件。因此，转录/RNA稳定性的定量变化和剪接比率的定性差异可以组合来表征肿瘤发生程序，并且签名mRNA同种型可以用作肿瘤诊断和预后的独特生物标志物。
The expression of specific mRNA isoforms may uniquely reflect the biological state of a cell because it reflects the integrated outcome of both transcriptional and posttranscriptional regulation. In this study, we constructed a splicing array to examine similar to 1,500 mRNA isoforms from a panel of genes previously implicated in prostate cancer and identified a large number of cell type-specific mRNA isoforms. We also developed a novel "two-dimensional" profiling strategy to simultaneously quantify changes in splicing and transcript abundance; the results revealed extensive covariation between transcription and splicing in prostate cancer cells. Taking advantage of the ability of our technology to analyze RNA from formalin-fixed, paraffin-embedded tissues, we derived a specific set of mRNA isoform biomarkers for prostate cancer using independent panels of tissue samples for feature selection and cross-analysis. A number of cancer-specific splicing switch events were further validated by laser capture microdissection. Quantitative changes in transcription/RNA stability and qualitative differences in splicing ratio may thus be combined to characterize tumorigenic programs and signature mRNA isoforms may serve as unique biomarkers for tumor diagnosis and prognosis.