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

Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik; Søkilde, Rolf LU ; Christensen, Ib Jarle; Hansen, Ulla; Brünner, Nils; Baker, Adam; Møller, Søren and Nielsen, Hans Jørgen (2011) In Clinical and Experimental Metastasis 28(1). p.27-38
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... (More)

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.

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published
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
in
Clinical and Experimental Metastasis
volume
28
issue
1
pages
12 pages
publisher
Springer
external identifiers
  • scopus:79951671912
ISSN
1573-7276
DOI
10.1007/s10585-010-9355-7
language
English
LU publication?
no
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25f7235d-8ee6-467d-bcd1-2b2941815cc9
date added to LUP
2017-09-01 14:32:16
date last changed
2017-11-12 04:34:53
@article{25f7235d-8ee6-467d-bcd1-2b2941815cc9,
  abstract     = {<p>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.</p>},
  author       = {Nielsen, Boye Schnack and Jørgensen, Stine and Fog, Jacob Ulrik and Søkilde, Rolf and Christensen, Ib Jarle and Hansen, Ulla and Brünner, Nils and Baker, Adam and Møller, Søren and Nielsen, Hans Jørgen},
  issn         = {1573-7276},
  keyword      = {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},
  language     = {eng},
  number       = {1},
  pages        = {27--38},
  publisher    = {Springer},
  series       = {Clinical and Experimental Metastasis},
  title        = {High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients},
  url          = {http://dx.doi.org/10.1007/s10585-010-9355-7},
  volume       = {28},
  year         = {2011},
}