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Cellular Oncology
Volume 31 (2009), Issue 1, Pages 19-29
http://dx.doi.org/10.3233/CLO-2009-0458

Potential Biomarkers of Colorectal Adenoma–Dysplasia–Carcinoma Progression: mRNA Expression Profiling and In Situ Protein Detection on TMAs Reveal 15 Sequentially Upregulated and 2 Downregulated Genes

Orsolya Galamb,1,2 Ferenc Sipos,1 Sándor Spisák,1 Barnabás Galamb,1 Tibor Krenács,3 Gábor Valcz,1 Zsolt Tulassay,1,2 and Béla Molnár1,2

12nd Department of Medicine, Semmelweis University, Budapest, Hungary
2Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary
31st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Copyright © 2009 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: As most colorectal cancers (CRC) develop from villous adenomas, studying alterations in gene expression profiles across the colorectal adenoma–dysplasia–carcinoma sequence may yield potential biomarkers of disease progression.

Methods: Total RNA was extracted, amplified, and biotinylated from colonic biopsies of 15 patients with CRC, 15 with villous adenoma and 8 normal controls. Gene expression profiles were evaluated using HGU133Plus2.0 microarrays and disease progression associated data were validated with RT-PCR. The potential biomarkers were also tested at the protein level using tissue microarray samples of 103 independent and 16 overlapping patients.

Results: 17 genes were validated to show sequentially altered expression at mRNA level through the normal–adenoma–dysplasia–carcinoma progression. Prostaglandin-D2 receptor (PTGDR) and amnionless homolog (AMN) genes revealed gradually decreasing expression while the rest of 15 genes including osteonectin, osteopontin, collagen IV–alpha 1, biglycan, matrix GLAprotein, and von Willebrand factor demonstrated progressively increasing expression. Similar trends of expression were confirmed at protein level for PTGDR, AMN, osteopontin and osteonectin.

Conclusion: Downregulated AMN and PTGDR and upregulated osteopontin and osteonectin were found as potential biomarkers of colorectal carcinogenesis and disease progression to be utilized for prospective biopsy screening both at mRNA and protein levels. Gene alterations identified here may also add to our understanding of CRC progression.