Applied Cellular and Molecular Biology PhD Program, Agricultural and Forestry Sciences Faculty. Universidad de La Frontera, Temuco, 4811230, Chile; Creative BioScience, Santiago, 8580702, Chile.
Int J Cancer. 2014 Feb 15;134(4):755-64. doi: 10.1002/ijc.28405. Epub 2013 Aug 29.
Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer.
研究低丰度转录组对于确定肿瘤进展的内在机制至关重要，这些机制可能为新的治疗方法提供依据。本研究旨在通过分析低丰度转录组，鉴定晚期人类胃癌中的新型标志物和可靶向基因及通路。该方法包括初始的消减杂交步骤，然后使用微阵列进行全基因表达分析。我们观察到低丰度转录组和全转录组之间在单个基因和基因本体水平上存在显著差异。低丰度转录组分析导致了新的生物标志物的鉴定和验证，如 LAMA3 和 TTN，通过组织微阵列进行；此外，我们还鉴定了癌症特异性的细胞内通路和可靶向基因，如 IRS2、IL17、IFNγ、VEGF-C、WISP1、FZD5 和 CTBP1，这些基因在全转录组分析中无法检测到。我们还证明了下调 CTBP1 的表达可使胃癌细胞对主要化疗药物敏感。我们的结论是，低丰度转录组的分析为癌症的分子基础和治疗提供了有用的见解。
