Department of Research and Development, GenomeDx Biosciences Inc., Vancouver, BC, Canada V6J 1J8.
J Oncol. 2012;2012:541353. doi: 10.1155/2012/541353. Epub 2012 Aug 16.
Prostate cancer is a clinically and biologically heterogeneous disease. Deregulation of splice variants has been shown to contribute significantly to this complexity. High-throughput technologies such as oligonucleotide microarrays allow for the detection of transcripts that play a role in disease progression in a transcriptome-wide level. In this study, we use a publicly available dataset of normal adjacent, primary tumor, and metastatic prostate cancer samples (GSE21034) to detect differentially expressed coding and non-coding transcripts between these disease states. To achieve this, we focus on transcript-specific probe selection regions, that is, those probe sets that correspond unambiguously to a single transcript. Based on this, we are able to pinpoint at the transcript-specific level transcripts that are differentially expressed throughout prostate cancer progression. We confirm previously reported cases and find novel transcripts for which no prior implication in prostate cancer progression has been made. Furthermore, we show that transcript-specific differential expression has unique prognostic potential and provides a clinically significant source of biomarker signatures for prostate cancer risk stratification. The results presented here serve as a catalog of differentially expressed transcript-specific markers throughout prostate cancer progression that can be used as basis for further development and translation into the clinic.
前列腺癌是一种临床上和生物学上具有异质性的疾病。剪接变体的失调已被证明对这种复杂性有重大贡献。高通量技术，如寡核苷酸微阵列，允许在转录组水平上检测在疾病进展中起作用的转录本。在这项研究中，我们使用了一个公开的正常相邻、原发性肿瘤和转移性前列腺癌样本数据集（GSE21034），以检测这些疾病状态之间差异表达的编码和非编码转录本。为了实现这一目标，我们专注于转录本特异性探针选择区域，即那些明确对应单个转录本的探针集。基于此，我们能够在转录本特异性水平上确定在整个前列腺癌进展过程中差异表达的转录本。我们证实了先前报道的病例，并发现了一些以前没有报道过与前列腺癌进展有关的新转录本。此外，我们还表明，转录本特异性差异表达具有独特的预后潜力，并为前列腺癌风险分层的生物标志物特征提供了有临床意义的来源。这里呈现的结果是整个前列腺癌进展过程中差异表达的转录本特异性标记物的目录，可作为进一步开发和转化为临床应用的基础。
