Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front

Publication: Research - peer-reviewJournal article – Annual report year: 2018

DOI

  • Author: Jepsen, Rikke Karlin

    University of Copenhagen, Denmark

  • Author: Novotny, Guy Wayne

    University of Copenhagen, Denmark

  • Author: Klarskov, Louise Laurberg

    University of Copenhagen, Denmark

  • Author: Bang-Bertelsen, Claus Heiner

    Research Group for Microbial Biotechnology and Biorefining, National Food Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Haakansson, Ida Trondhjem

    Medical Prognosis Institute A/S, Denmark

  • Author: Hansen, Anker

    Medical Prognosis Institute A/S, Denmark

  • Author: Christensen, Ib Jarle

    University of Copenhagen, Denmark

  • Author: Ass, Lene Buhl Riis

    University of Copenhagen, Denmark

  • Author: Høgdall, Estrid

    University of Copenhagen, Denmark

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Accurate prediction of regional lymph node metastases (LNM) in endoscopically resected pT1 colorectal cancer (CRC) is crucial in treatment stratification for subsequent radical surgery. Several miRNAs have been linked to CRC invasion and metastasis, including the oncogenic miR-17/92 cluster, and expression levels might have predictive value in the risk assessment of early metastatic progression in CRC. We performed global miRNA microarray using tissue samples from the invasive front of pT1 CRC and investigated associations of the miR-17/92 cluster and presence of LNM.

In total, 56 matched pT1 CRCs were thoroughly clinico-pathologically characterized and miRNA microarrays were performed on invasive front tissue samples. Global miRNA intensities were screened using paired t-tests between pT1pN+ and pT1pN0. Associations between miR-17/92 and histopathological features were analyzed using general linear models and tumor cell adjusted expression intensities.

miR-17-3p and miR-92a were significantly higher expressed in the invasive front of tumors with LNM compared to those without, corresponding to 1.53 fold higher expression of miR-17-3p (95%CI: 1.04–2.24, P = .030) and 1.28 fold higher expression of miR-92a (95%CI: 1.01–1.68, P = .042). An inverse association between miR-19a and presence of high grade tumor budding was observed (1.55 fold, 95%CI: 1.13–2.12, P = .008). We provide evidence for associations between early regional LNM and high expression levels of the miR-17/92 cluster members: miR-17-3p and miR-92a, in the invasive front of CRC. Our results support a role for the miR-17/92 cluster in early metastatic progression of CRC and calls for further investigation.
Original languageEnglish
JournalHuman Pathology
ISSN0046-8177
DOIs
StateAccepted/In press - 2018
CitationsWeb of Science® Times Cited: No match on DOI

    Keywords

  • Colorectal Cancer, pT1, Invasive Tumor Front, Metastases, Microarray, microRNA, miR-17/92
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