A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue
- Shuyang Wang1,
- Lei Wang1,
- Nayima Bayaxi1,
- Jian Li2,
- Wim Verhaegh3,
- Angel Janevski4,
- Vinay Varadan4,
- Yiping Ren2,
- Dennis Merkle3,
- Xianxin Meng5,
- Xue Gao6,
- Huijun Wang6,
- Jiaqiang Ren7,
- Winston Patrick Kuo8,
- Nevenka Dimitrova4,
- Ying Wu1,2,
- Hongguang Zhu1,6,9
- 1Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
- 2Department of Healthcare, Philips Research Asia – Shanghai, Shanghai, China
- 3Department of Molecular Diagnostics, Philips Research, Eindhoven, The Netherlands
- 4Philips Research North America, New York, USA
- 5Shanghai Biochip Company, Shanghai, China
- 6Institute of Biomedical Sciences, Fudan University, Shanghai, China
- 7Department of Transfusion Medicine, Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
- 8Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA
- 9Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai, China
- Correspondence to Professor Hongguang Zhu, Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China; Dr Ying Wu, Philips Research Asia – Shanghai, 888 Tian Lin Road Shanghai 200233, China; Dr Nevenka Dimitrova, Philips Research North America, 345 Scarborough Road Briarcliff Manor, NY10510, USA;
Contributors SW, ND, YW, HZ: study design, data interpretation and intellectual content. HW: tissue bank and patient database. SW, LW, NB, YR, XM, XG: acquisition of experimental data. JL, WV, AJ, VV, JR, ND: data analysis. SW, HZ: drafting of manuscript. WPK, EG, DM, YW, ND: critical revision of manuscript. HZ, YW, ND: funding support.
- Revised 7 January 2012
- Accepted 13 January 2012
- Published Online First 25 April 2012
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.
- Colorectal carcinoma
- colorectal cancer genes
- colorectal pathology
- gastrointestinal cancer
- gastrointestinal pathology
- gastric epithelial cell function
- cell signalling
- colon carcinogenesis
- colorectal cancer
- cancer genetics
- cell biology
- genetic testing
- molecular pathology
- signal transduction
- clinical decision making
- gene expression
- molecular biology
SW and LW contributed equally to this work.
Funding This work was supported by grants from Philips Company Research (2007-062) and from Science and Technology Commission of Shanghai Municipality (06DZ22904).
Correction notice This article has been corrected since it was published Online First. The statement ‘SW and LW contributed equally to this work’ has been included.
Competing interests None.
Patient consent Obtained.
Ethics approval The institutional review board of Shanghai Medical College in Fudan University.
Provenance and peer review Not commissioned; externally peer reviewed.