Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis

Background: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. Methods: Tumour stroma was isolated from formalin-fixed, paraffin-e...

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Published inBritish journal of cancer Vol. 117; no. 9; pp. 1360 - 1370
Main Authors Murakami, Tomohiro, Kikuchi, Hirotoshi, Ishimatsu, Hisato, Iino, Ichirota, Hirotsu, Amane, Matsumoto, Tomohiro, Ozaki, Yusuke, Kawabata, Toshiki, Hiramatsu, Yoshihiro, Ohta, Manabu, Kamiya, Kinji, Fukushima, Mayu, Baba, Satoshi, Kitagawa, Kyoko, Kitagawa, Masatoshi, Konno, Hiroyuki
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 24.10.2017
Nature Publishing Group
Subjects
1885/67/1504/1885
631/67/1857
631/67/327
Aged
Bioindicators
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Drug Resistance
Epidemiology
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Laser arrays
Liver
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - secondary
Lymphatic Metastasis
Male
Medical prognosis
Metastases
Metastasis
MicroRNAs - genetics
miRNA
Molecular Diagnostics
Molecular Medicine
Neoplasm Invasiveness
Neoplasm Staging
Oncology
Paraffin
Prognosis
Staining
Stroma
Stromal Cells - metabolism
Stromal Cells - pathology
Survival
Survival Rate
Tenascin
Tenascin - metabolism
Tenascin C
Tissues
Tumor Cells, Cultured
Tumors
liver metastasis
colorectal cancer
tumour stroma
prognostic markers
miR-198
microRNA
tenascin C
Online AccessGet full text

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Abstract Background: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. Methods: Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. Results: Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis ( P <0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival ( P =0.005; n =139) and liver metastasis-free survival ( P =0.001; n =128). Conclusions: Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
AbstractList Background:Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis.Methods:Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays.Results:Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128).Conclusions:Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
BACKGROUNDTumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis.METHODSTumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays.RESULTSHierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128).CONCLUSIONSAlterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
Background: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. Methods: Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. Results: Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis ( P <0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival ( P =0.005; n =139) and liver metastasis-free survival ( P =0.001; n =128). Conclusions: Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128). Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.
Author Kitagawa, Masatoshi
Iino, Ichirota
Ozaki, Yusuke
Hirotsu, Amane
Kikuchi, Hirotoshi
Matsumoto, Tomohiro
Kitagawa, Kyoko
Murakami, Tomohiro
Ohta, Manabu
Ishimatsu, Hisato
Kawabata, Toshiki
Baba, Satoshi
Konno, Hiroyuki
Hiramatsu, Yoshihiro
Kamiya, Kinji
Fukushima, Mayu
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  organization: Second Department of Surgery, Hamamatsu University School of Medicine
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  organization: Second Department of Surgery, Hamamatsu University School of Medicine
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  organization: Second Department of Surgery, Hamamatsu University School of Medicine
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  givenname: Manabu
  surname: Ohta
  fullname: Ohta, Manabu
  organization: Oncology Center, Hamamatsu University School of Medicine
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  surname: Kamiya
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  organization: Second Department of Surgery, Hamamatsu University School of Medicine
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  surname: Fukushima
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  organization: Department of Pathology, Hamamatsu University School of Medicine
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  surname: Baba
  fullname: Baba, Satoshi
  organization: Department of Pathology, Hamamatsu University School of Medicine
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  surname: Kitagawa
  fullname: Kitagawa, Kyoko
  organization: Department of Molecular Biology, Hamamatsu University School of Medicine
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  surname: Kitagawa
  fullname: Kitagawa, Masatoshi
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  surname: Konno
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  organization: Second Department of Surgery, Hamamatsu University School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29065427$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright The Author(s) 2017
Copyright Nature Publishing Group Oct 24, 2017
Copyright © 2017 Cancer Research UK 2017 Cancer Research UK
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Issue 9
Keywords liver metastasis
colorectal cancer
tumour stroma
prognostic markers
miR-198
microRNA
tenascin C
Language English
License From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0
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Snippet Background: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and...
Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their...
Background:Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and...
BACKGROUNDTumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and...
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springer
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StartPage 1360
SubjectTerms 1885/67/1504/1885
631/67/1857
631/67/327
Aged
Bioindicators
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Drug Resistance
Epidemiology
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Laser arrays
Liver
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - secondary
Lymphatic Metastasis
Male
Medical prognosis
Metastases
Metastasis
MicroRNAs - genetics
miRNA
Molecular Diagnostics
Molecular Medicine
Neoplasm Invasiveness
Neoplasm Staging
Oncology
Paraffin
Prognosis
Staining
Stroma
Stromal Cells - metabolism
Stromal Cells - pathology
Survival
Survival Rate
Tenascin
Tenascin - metabolism
Tenascin C
Tissues
Tumor Cells, Cultured
Tumors
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Title Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis
URI https://link.springer.com/article/10.1038/bjc.2017.291
https://www.ncbi.nlm.nih.gov/pubmed/29065427
https://www.proquest.com/docview/1955042955
https://search.proquest.com/docview/1955605710
https://pubmed.ncbi.nlm.nih.gov/PMC5672932
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