The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

Jochen Gaedcke; Marian Grade; Jordi Camps; Rolf Søkilde; Bogumil Kaczkowski; Aaron J. Schetter; Michael J. Difilippantonio; Curtis C. Harris; B. Michael Ghadimi; Søren Møller; Tim Beissbarth; Thomas Ried; Thomas Litman

doi:10.1158/1078-0432.ccr-12-0016

The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

Jochen Gaedcke, Marian Grade, Jordi Camps, Rolf Søkilde, Bogumil Kaczkowski, Aaron J. Schetter, Michael J. Difilippantonio, Curtis C. Harris, B. Michael Ghadimi, Søren Møller, Tim Beissbarth, Thomas Ried, Thomas Litman

139 Citationer (Scopus)

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 validated using semi-quantitative real-time PCR. Results: Forty-nine miRNAs were significantly differentially expressed (log2-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.

Originalsprog	Engelsk
Tidsskrift	Clinical Cancer Research
Vol/bind	18
Udgave nummer	18
Sider (fra-til)	4919-4930
Antal sider	12
ISSN	1078-0432
DOI	https://doi.org/10.1158/1078-0432.ccr-12-0016
Status	Udgivet - 15 sep. 2012

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10.1158/1078-0432.ccr-12-0016

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Gaedcke, J., Grade, M., Camps, J., Søkilde, R., Kaczkowski, B., Schetter, A. J., Difilippantonio, M. J., Harris, C. C., Ghadimi, B. M., Møller, S., Beissbarth, T., Ried, T., & Litman, T. (2012). The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa. Clinical Cancer Research, 18(18), 4919-4930. https://doi.org/10.1158/1078-0432.ccr-12-0016

Gaedcke, J, Grade, M, Camps, J, Søkilde, R, Kaczkowski, B, Schetter, AJ, Difilippantonio, MJ, Harris, CC, Ghadimi, BM, Møller, S, Beissbarth, T, Ried, T & Litman, T 2012, 'The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa', Clinical Cancer Research, bind 18, nr. 18, s. 4919-4930. https://doi.org/10.1158/1078-0432.ccr-12-0016

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title = "The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa",

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 validated using semi-quantitative real-time PCR. Results: Forty-nine miRNAs were significantly differentially expressed (log2-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.",

keywords = "Cluster Analysis, Colonic Neoplasms, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Intestinal Mucosa, MicroRNAs, Prognosis, Rectal Neoplasms, Rectum, Reproducibility of Results",

author = "Jochen Gaedcke and Marian Grade and Jordi Camps and Rolf S{\o}kilde and Bogumil Kaczkowski and Schetter, {Aaron J.} and Difilippantonio, {Michael J.} and Harris, {Curtis C.} and Ghadimi, {B. Michael} and S{\o}ren M{\o}ller and Tim Beissbarth and Thomas Ried and Thomas Litman",

note = "{\textcopyright}2012 AACR.",

year = "2012",

month = sep,

day = "15",

doi = "10.1158/1078-0432.ccr-12-0016",

language = "English",

volume = "18",

pages = "4919--4930",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research (A A C R)",

number = "18",

}

TY - JOUR

T1 - The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

AU - Gaedcke, Jochen

AU - Grade, Marian

AU - Camps, Jordi

AU - Søkilde, Rolf

AU - Kaczkowski, Bogumil

AU - Schetter, Aaron J.

AU - Difilippantonio, Michael J.

AU - Harris, Curtis C.

AU - Ghadimi, B. Michael

AU - Møller, Søren

AU - Beissbarth, Tim

AU - Ried, Thomas

AU - Litman, Thomas

PY - 2012/9/15

Y1 - 2012/9/15

N2 - 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 (log2-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.

AB - 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 (log2-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.

KW - Cluster Analysis

KW - Colonic Neoplasms

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Gene Regulatory Networks

KW - Humans

KW - Intestinal Mucosa

KW - MicroRNAs

KW - Prognosis

KW - Rectal Neoplasms

KW - Rectum

KW - Reproducibility of Results

U2 - 10.1158/1078-0432.ccr-12-0016

DO - 10.1158/1078-0432.ccr-12-0016

M3 - Journal article

C2 - 22850566

SN - 1078-0432

VL - 18

SP - 4919

EP - 4930

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 18

ER -

The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

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