A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue. Issue 2 (25th April 2012)

• Record Type: Journal Article
• Authors: Wang, Shuyang; Wang, Lei; Bayaxi, Nayima; Li, Jian; Verhaegh, Wim; Janevski, Angel; Varadan, Vinay; Ren, Yiping; Merkle, Dennis; Meng, Xianxin; Gao, Xue; Wang, Huijun; Ren, Jiaqiang; Kuo, Winston Patrick; Dimitrova, Nevenka; Wu, Ying; Zhu, Hongguang
• Is Part Of: Gut. Volume 62:Issue 2(2013)
• Page Start: 280
• Page End: 289
• Publication Date: 2012-04-25
• Subjects: Colorectal carcinoma -- colorectal cancer genes -- colorectal pathology -- gastrointestinal cancer -- gastrointestinal pathology -- genetics -- gastric epithelial cell function -- cancer -- cell signalling -- colon carcinogenesis -- colorectal cancer -- cancer genetics -- cell biology -- genetic testing -- molecular pathology -- signal transduction -- clinical decision making -- gene expression -- molecular biology -- genes; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2011-301554
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: It is a challenge to differentiate invasive carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues. In this study, microRNA profiles were evaluated in the transformation of colorectal carcinogenesis to discover new molecular markers for identifying a carcinoma in colonoscopy biopsy tissues where the presence of stromal invasion cells is not detectable by microscopic analysis. Methods: The expression of 723 human microRNAs was measured in laser capture microdissected epithelial tumours from 133 snap-frozen surgical colorectal specimens. Three well-known classification algorithms were used to derive candidate biomarkers for discriminating carcinomas from adenomas. Quantitative reverse-transcriptase PCR was then used to validate the candidates in an independent cohort of macrodissected formalin-fixed paraffin-embedded colorectal tissue samples from 91 surgical resections. The biomarkers were applied to differentiate carcinomas from high-grade intraepithelial neoplasms in 58 colonoscopy biopsy tissue samples with stromal invasion cells undetectable by microscopy. Results: One classifier of 14 microRNAs was identified with a prediction accuracy of 94.1% for discriminating carcinomas from adenomas. In formalin-fixed paraffin-embedded surgical tissue samples, a combination of miR-375, miR-424 and miR-92a yielded an accuracy of 94% (AUC=0.968) in discriminating carcinomas from adenomas. This combination has been applied to differentiate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues with an accuracy of 89% (AUC=0.918). Conclusions: This study has found a microRNA panel that accurately discriminates carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissues. This microRNA panel has considerable clinical value in the early diagnosis and optimal surgical decision-making of colorectal cancer.