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. CONCLUSIONS: 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.
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. CONCLUSIONS: 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.
Authors: Gábor Valcz; Ferenc Sipos; Tibor Krenács; Jeannette Molnár; Arpád V Patai; Katalin Leiszter; Kinga Tóth; Norbert Solymosi; Orsolya Galamb; Béla Molnár; Zsolt Tulassay Journal: Pathol Oncol Res Date: 2010-03-27 Impact factor: 3.201
Authors: Achilleas D Theocharis; Spyros S Skandalis; Thomas Neill; Hinke A B Multhaupt; Mario Hubo; Helena Frey; Sandeep Gopal; Angélica Gomes; Nikos Afratis; Hooi Ching Lim; John R Couchman; Jorge Filmus; Ralph D Sanderson; Liliana Schaefer; Renato V Iozzo; Nikos K Karamanos Journal: Biochim Biophys Acta Date: 2015-03-28
Authors: Paul A Keire; Steven L Bressler; Eileen R Mulvihill; Barry C Starcher; Inkyung Kang; Thomas N Wight Journal: Matrix Biol Date: 2015-12-23 Impact factor: 11.583
Authors: Brigette L Tippin; A Joan Levine; Alicia M Materi; Wen-Liang Song; Temitope O Keku; Julie E Goodman; Leah B Sansbury; Sudipto Das; Aihua Dai; Alan M Kwong; Amy M Lin; John M Lin; Jae Man Park; Ruth E Patterson; Rowan T Chlebowski; R Michael Garavito; Tsuyoshi Inoue; Wonhwa Cho; John A Lawson; Shiv Kapoor; Laurence N Kolonel; Loïc Le Marchand; Robert W Haile; Robert S Sandler; Henry J Lin Journal: Prostaglandins Other Lipid Mediat Date: 2011-07-28 Impact factor: 3.072
Authors: Michal Mikula; Tymon Rubel; Jakub Karczmarski; Krzysztof Goryca; Michal Dadlez; Jerzy Ostrowski Journal: Funct Integr Genomics Date: 2010-11-09 Impact factor: 3.410
Authors: O Galamb; S Spisák; F Sipos; K Tóth; N Solymosi; B Wichmann; T Krenács; G Valcz; Z Tulassay; B Molnár Journal: Br J Cancer Date: 2010-01-19 Impact factor: 7.640