High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

Research output: Contribution to journalArticle

Abstract

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short disease-free survival.

Details

Authors
  • Boye Schnack Nielsen
  • Stine Jørgensen
  • Jacob Ulrik Fog
  • Rolf Søkilde
  • Ib Jarle Christensen
  • Ulla Hansen
  • Nils Brünner
  • Adam Baker
  • Søren Møller
  • Hans Jørgen Nielsen
External organisations
  • Exiqon A/S
Research areas and keywords

Keywords

  • Aged, Aged, 80 and over, Colorectal Neoplasms, DNA Probes, Disease-Free Survival, Female, Humans, In Situ Hybridization, Fluorescence, Male, MicroRNAs, Multivariate Analysis, Neoplasm Staging, Oligonucleotides, Predictive Value of Tests, Prognosis, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Stromal Cells, Time Factors, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalClinical and Experimental Metastasis
Volume28
Issue number1
Publication statusPublished - 2011 Jan
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes