title: A microRNA panel to discriminate carcinomas from high-grade intraepithelial neoplasms in colonoscopy biopsy tissue.
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.
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Nayima
authors.initials: N
authors.lastname: Bayaxi
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Wim
authors.initials: W
authors.lastname: Verhaegh
authors.forename: Angel
authors.initials: A
authors.lastname: Janevski
authors.forename: Vinay
authors.initials: V
authors.lastname: Varadan
authors.forename: Yiping
authors.initials: Y
authors.lastname: Ren
authors.forename: Dennis
authors.initials: D
authors.lastname: Merkle
authors.forename: Xianxin
authors.initials: X
authors.lastname: Meng
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Ren
authors.forename: Winston Patrick
authors.initials: WP
authors.lastname: Kuo
authors.forename: Nevenka
authors.initials: N
authors.lastname: Dimitrova
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Hongguang
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000235:genetics; D016000:Cluster Analysis; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D061346:Laser Capture Microdissection; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs