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

Rikke Karlin Jepsen*, Guy Wayne Novotny, Louise Laurberg Klarskov, Claus Heiner Bang-Bertelsen, Ida Trondhjem Haakansson, Anker Hansen, Ib Jarle Christensen, Lene Buhl Riis Ass, Estrid Høgdall

*Corresponding author for this work

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Abstract

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
Volume80
Pages (from-to)231-238
ISSN0046-8177
DOIs
Publication statusPublished - 2018

Keywords

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

Cite this

Jepsen, Rikke Karlin ; Novotny, Guy Wayne ; Klarskov, Louise Laurberg ; Bang-Bertelsen, Claus Heiner ; Haakansson, Ida Trondhjem ; Hansen, Anker ; Christensen, Ib Jarle ; Ass, Lene Buhl Riis ; Høgdall, Estrid. / Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front. In: Human Pathology. 2018 ; Vol. 80. pp. 231-238.
@article{c20d39cbef7e49feac29043605e770b9,
title = "Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front",
abstract = "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.",
keywords = "Colorectal Cancer, pT1, Invasive Tumor Front, Metastases, Microarray, microRNA, miR-17/92",
author = "Jepsen, {Rikke Karlin} and Novotny, {Guy Wayne} and Klarskov, {Louise Laurberg} and Bang-Bertelsen, {Claus Heiner} and Haakansson, {Ida Trondhjem} and Anker Hansen and Christensen, {Ib Jarle} and Ass, {Lene Buhl Riis} and Estrid H{\o}gdall",
year = "2018",
doi = "10.1016/j.humpath.2018.05.027",
language = "English",
volume = "80",
pages = "231--238",
journal = "Human Pathology",
issn = "0046-8177",
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Jepsen, RK, Novotny, GW, Klarskov, LL, Bang-Bertelsen, CH, Haakansson, IT, Hansen, A, Christensen, IJ, Ass, LBR & Høgdall, E 2018, 'Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front', Human Pathology, vol. 80, pp. 231-238. https://doi.org/10.1016/j.humpath.2018.05.027

Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front. / Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg; Bang-Bertelsen, Claus Heiner; Haakansson, Ida Trondhjem; Hansen, Anker; Christensen, Ib Jarle; Ass, Lene Buhl Riis; Høgdall, Estrid.

In: Human Pathology, Vol. 80, 2018, p. 231-238.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front

AU - Jepsen, Rikke Karlin

AU - Novotny, Guy Wayne

AU - Klarskov, Louise Laurberg

AU - Bang-Bertelsen, Claus Heiner

AU - Haakansson, Ida Trondhjem

AU - Hansen, Anker

AU - Christensen, Ib Jarle

AU - Ass, Lene Buhl Riis

AU - Høgdall, Estrid

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Colorectal Cancer

KW - pT1

KW - Invasive Tumor Front

KW - Metastases

KW - Microarray

KW - microRNA

KW - miR-17/92

U2 - 10.1016/j.humpath.2018.05.027

DO - 10.1016/j.humpath.2018.05.027

M3 - Journal article

VL - 80

SP - 231

EP - 238

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

ER -