Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland.
BMC Cancer. 2010 Dec 20;10:687. doi: 10.1186/1471-2407-10-687.
To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome.
DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information.
The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance.
Analysis from our in vitro and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including IGF2BP2, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear; however, the numbers that have been detected by the disease-specific microarray would suggest that they may be important regulatory transcripts. This study has demonstrated the power of a disease-specific transcriptome-based approach and highlighted the potential novel biologically and clinically relevant information that is gained when using such a methodology.
迄今为止，对于晚期结直肠癌的现有治疗方案，尚无临床可靠的预测反应标志物。本研究的目的是比较和评估使用通用微阵列和基于疾病特异性转录组的微阵列进行转录谱分析的能力。我们还研究了疾病特异性转录组的生物学和临床相关性。
使用 Affymetrix HG-U133 Plus2.0 阵列和 Almac Diagnostics 结直肠癌疾病特异性研究工具，对同源敏感和 5-FU 耐药 HCT116 结直肠癌细胞系进行 DNA 微阵列分析。此外，还使用结直肠癌疾病特异性研究工具对预处理转移性结直肠癌活检进行 DNA 微阵列分析。基于检测探针和生物学信息，比较了两种微阵列平台。
结果表明，在多个层面上，基于疾病特异性转录组的微阵列能够优于通用基因组微阵列，包括检测转录物和途径分析。此外，疾病特异性微阵列包含大量反义转录物，进一步分析表明其中一些存在于 sense:antisense 对中。细胞系模型和转移性 CRC 患者活检之间的比较进一步表明，在 CRC 患者活检中也检测到了许多已识别的 sense:antisense 对，这表明其具有潜在的临床相关性。
我们的体外和临床实验分析表明，许多转录物存在于 sense:antisense 对中，包括 IGF2BP2，其在结直肠癌的背景下可能具有直接的调节功能。尽管许多研究已经证实了反义转录物的功能相关性，但它们的功能作用目前尚不清楚；然而，疾病特异性微阵列检测到的反义转录物数量表明它们可能是重要的调节转录物。本研究证明了基于疾病特异性转录组的方法的有效性，并强调了使用这种方法获得的潜在新颖的生物学和临床相关信息。
