title: The colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information.
abstract: 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 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.
  
  
  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.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Allen
authors.forename: Puthen V
authors.initials: PV
authors.lastname: Jithesh
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Oliver
authors.forename: Irina
authors.initials: I
authors.lastname: Proutski
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Longley
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Vitali
authors.initials: V
authors.lastname: Proutski
authors.forename: Paul
authors.initials: P
authors.lastname: Harkin
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Johnston
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001706:Biopsy; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D045325:HCT116 Cells; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D016372:RNA, Antisense / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000964:Antimetabolites, Antineoplastic; D018971:Insulin-Like Growth Factor Binding Protein 2; D016372:RNA, Antisense; D005472:Fluorouracil