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Molecular profiling of ulcerative colitis-associated neoplastic progression
Daniel W Colliver1, Nigel P S Crawford, Maurice R Eichenberger
1Digestive Surgery Research Laboratory, Price Institute for Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA. danielcolliver@hotmail.com
Experimental and Molecular Pathology
|November 10, 2005
Summary
Researchers identified 699 genes with altered expression during ulcerative colitis (UC) dysplasia development and 392 during progression to adenocarcinoma. These findings offer potential biomarkers for early diagnosis of UC-associated colorectal cancer.
Area of Science:
- Molecular biology
- Oncology
- Gastroenterology
Background:
- Ulcerative colitis (UC)-associated colorectal cancer differs fundamentally from sporadic forms.
- Transcriptional alterations in UC-associated neoplasia progression are not well-described.
Purpose of the Study:
- To characterize gene expression changes during neoplastic progression in UC.
- To identify potential biomarkers for early diagnosis of UC-associated colorectal cancer.
Main Methods:
- Affymetrix U95Av2 microarrays were used to assess differential gene expression.
- Mixed statistical models correlated transcript alterations across benign UC, UC-dysplasia, and UC adenocarcinoma tissues.
- Quantitative real-time reverse-transcription polymerase chain reaction validated key transcript alterations.
Main Results:
- 699 genes showed altered expression with dysplasia development.
- 392 transcripts were differentially expressed in progression to adenocarcinoma.
- 224 transcripts were common to both dysplasia and adenocarcinoma stages.
- Many differentially expressed genes, including those involved in cell proliferation, apoptosis, signal transduction, and DNA repair, were previously unknown in UC neoplasia.
Conclusions:
- Distinct molecular events may drive UC-associated neoplasia compared to sporadic colorectal cancer.
- Several identified genes show similar expression changes in dysplastic and cancerous tissues, suggesting roles in early cancer formation.
- These genes represent potential clinical biomarkers for improved early diagnosis of UC-associated colorectal cancer.