The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer

Abstract

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. What's new? The present study aimed to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analysis of the low-abundance transcriptome. Aberrant cancer-specific intracellular pathways such as the wnt/hedgehog and the PI3K and genes like CTBP1 were identified. Most of the differentially expressed low-abundance transcripts were not detected when the whole transcriptome was analyzed. CTBP1 was further identified as a novel target for sensitization of gastric cancer cells to chemotherapeutic drugs that have shown limited effectiveness in the clinics. The study of the low-abundance transcriptome might help to improve response to mainstay treatments and develop novel therapies. © 2013 UICC.