MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease

Int J Colorectal Dis. 2011 Nov;26(11):1415-22. doi: 10.1007/s00384-011-1279-4. Epub 2011 Jul 8.

Abstract

Purpose: Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters.

Methods: Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages.

Results: Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease.

Conclusion: Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Staging
  • Neural Networks, Computer
  • Polymerase Chain Reaction
  • Reproducibility of Results

Substances

  • MicroRNAs