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COLON CANCER |
1 Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby Hospital, Aarhus N, Denmark
2 Institute of Pathology, Aarhus University Hospital, Aarhus Sygehus, Aarhus C, Denmark
3 Surgical Department L, Aarhus University Hospital, Aarhus Sygehus, Aarhus C, Denmark
4 Department of Medical Genetics, Biomedicum, University of Helsinki, Helsinki, Finland
Correspondence to:
Correspondence to:
Professor T F Ørntoft
Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital/Skejby, Brendstrupgaardsvej 100, DK- 8200 Aarhus N, Denmark; orntoft{at}ki.au.dk
ABSTRACT
Background and aims: There are epidemiological, morphological, and molecular differences between normal mucosa as well as between adenocarcinomas of the right and left side of the large bowel. The aim of this study was to investigate differences in gene expression.
Methods: Oligonucleotide microarrays (GeneChip) were used to compare gene expression in 45 single samples from normal mucosa and sporadic colorectal carcinomas (Dukes’ B and C) of the caecum compared with the sigmoid and rectosigmoid. Findings were validated by real time polymerase chain reaction.
Results: Fifty eight genes were found to be differentially expressed between the normal mucosa of the caecum and the sigmoid and rectosigmoid (p<0.01), including pS2, S100P, and a sialyltransferase, all being expressed at higher levels in the caecum. A total of 118 and 186 genes were differentially expressed between normal and right or left sided tumours of the colon, showing more pronounced differences in Dukes’ C than B tumours. Thirty genes differentially expressed in tumour tissue were common to adenocarcinomas of both sides, including known tumour markers such as the matrix metalloproteinases. Keratins 8, 19, and 20 as well as carbonic anhydrases (II, IV, VII) showed side specific expression and were downregulated in left sided tumours whereas teratocarcinoma growth factor and cyclooxygenase 2 (COX-2) were upregulated in left sided adenocarcinomas. Immunohistochemical analysis confirmed differences in side specific expression for cytokeratin 20 and COX-2.
Conclusions: Differences in gene expression between normal mucosa as well as between adenocarcinomas of the caecum and sigmoid or rectosigmoid exist and should be taken into account when examining new targeted therapeutic regimens.
Abbreviations: LCC, left sided colon cancer; RCC, right sided colon cancer; UG cluster, UniGene cluster (http://www.ncbi.nlm.nih.gov/UniGene); EGFR, epidermal growth factor receptor; PCNA, proliferating cell nuclear antigen; DPP IV, dipeptidylpeptidase IV; RT-PCR, reverse transcription-polymerase chain reaction; COX-2, cyclooxygenase 2; MSS, microsatellite stable; CA, carbonic anhydrase; MMP, matrix metalloproteinase
Keywords: gene expression; colon cancer; caecum; sigmoid; rectosigmoid; large bowel; microarray; biomarkers
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