The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information
The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information
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DOI：
10.1186/1471-2407-10-687
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发表时间：
2010-12-20
期刊：
影响因子：
3.8
通讯作者：
Johnston, Patrick G.
中科院分区：
文献类型：
--
作者：
Allen, Wendy L.;Jithesh, Puthen V.;Johnston, Patrick G.
背景：到目前为止，还没有临床上可靠的预测标记物来预测对当前治疗方案的反应。目前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图谱分析的能力。方法：利用Affymetrix HG-U133 Plus2.0芯片和ALMAC结直肠癌疾病特异性研究工具，对同基因敏感和5-FU耐药的HCT116结直肠癌细胞株进行DNA芯片分析。此外，还使用结直肠癌疾病特异性研究工具对治疗前转移性结直肠癌活检组织进行了DNA微阵列分析。结果：结果表明，基于疾病特异性转录组的微阵列在转录本检测和通路分析等多个水平上均优于普通基因组微阵列。此外，疾病特异性微阵列包含高比例的反义转录本，进一步的分析表明，其中一些存在于正义：反义对中。细胞系模型和转移性结直肠癌患者活检组织的比较进一步表明，在结直肠癌患者活检组织中也检测到了一些已识别的正义：反义对，提示了潜在的临床意义。结论：我们的体外和临床实验分析表明，许多转录本都存在正义：反义对，包括IGF2BP2，它可能在结直肠癌背景下具有直接调节功能。虽然许多研究已经确定了反义转录本的功能相关性，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数字表明，它们可能是重要的调控转录本。这项研究证明了基于疾病特异性转录组的方法的力量，并强调了当使用这种方法时获得的潜在的生物和临床相关的新信息。
Background: 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.Methods: 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.Results: The results demonstrated that the disease-specific transcriptome-based microarray was able to outperform 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.Conclusions: 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.