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The Rectal Cancer microRNAome - microRNA Expression in Rectal Cancer and Matched Normal Mucosa.

Gaedcke, Jochen; Grade, Marian; Camps, Jordi; Sökilde, Rolf LU ; Kaczkowski, Bogumil; Schetter, Aaron J; Difilippantonio, Michael J; Harris, Curtis C; Ghadimi, B Michael and Møller, Søren, et al. (2012) In Clinical Cancer Research 18(18). p.4919-4930
Abstract
PURPOSE:

miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.



EXPERIMENTAL DESIGN:

Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was... (More)
PURPOSE:

miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.



EXPERIMENTAL DESIGN:

Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR.



RESULTS:

Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients.



CONCLUSION:

This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation. Clin Cancer Res; 1-12. ©2012 AACR. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
18
issue
18
pages
4919 - 4930
publisher
American Association for Cancer Research
external identifiers
  • wos:000309965700010
  • pmid:22850566
  • scopus:84866364068
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-12-0016
language
English
LU publication?
yes
id
862d1195-4ce2-4a51-8fca-b72ff4685764 (old id 3047883)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22850566?dopt=Abstract
date added to LUP
2012-09-03 22:01:57
date last changed
2017-10-22 04:53:22
@article{862d1195-4ce2-4a51-8fca-b72ff4685764,
  abstract     = {PURPOSE: <br/><br>
miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.<br/><br>
<br/><br>
EXPERIMENTAL DESIGN: <br/><br>
Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR.<br/><br>
<br/><br>
RESULTS: <br/><br>
Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference &gt;0.5 and P &lt; 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients.<br/><br>
<br/><br>
CONCLUSION: <br/><br>
This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation. Clin Cancer Res; 1-12. ©2012 AACR.},
  author       = {Gaedcke, Jochen and Grade, Marian and Camps, Jordi and Sökilde, Rolf and Kaczkowski, Bogumil and Schetter, Aaron J and Difilippantonio, Michael J and Harris, Curtis C and Ghadimi, B Michael and Møller, Søren and Beissbarth, Tim and Ried, Thomas and Litman, Thomas},
  issn         = {1078-0432},
  language     = {eng},
  number       = {18},
  pages        = {4919--4930},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {The Rectal Cancer microRNAome - microRNA Expression in Rectal Cancer and Matched Normal Mucosa.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-12-0016},
  volume       = {18},
  year         = {2012},
}