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ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer

Magnusson, Kristina; Gremel, Gabriela; Rydén, Lisa LU ; Pontén, Victor; Uhlén, Mathias; Dimberg, Anna; Jirström, Karin LU and Pontén, Fredrik LU (2016) In BMC Cancer 16(1).
Abstract

Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n=484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor... (More)

Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n=484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. Conclusions: ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANLN, Antibody-based proteomics, Breast cancer, Prognostic biomarker, Proliferation
in
BMC Cancer
volume
16
issue
1
publisher
BioMed Central
external identifiers
  • scopus:84998694458
  • wos:000388038200007
ISSN
1471-2407
DOI
10.1186/s12885-016-2923-8
language
English
LU publication?
yes
id
da699b64-2598-488a-b644-1ec4686051d4
date added to LUP
2016-12-19 13:03:41
date last changed
2017-10-01 05:27:48
@article{da699b64-2598-488a-b644-1ec4686051d4,
  abstract     = {<p>Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n=484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. Conclusions: ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.</p>},
  articleno    = {904},
  author       = {Magnusson, Kristina and Gremel, Gabriela and Rydén, Lisa and Pontén, Victor and Uhlén, Mathias and Dimberg, Anna and Jirström, Karin and Pontén, Fredrik},
  issn         = {1471-2407},
  keyword      = {ANLN,Antibody-based proteomics,Breast cancer,Prognostic biomarker,Proliferation},
  language     = {eng},
  month        = {11},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer},
  url          = {http://dx.doi.org/10.1186/s12885-016-2923-8},
  volume       = {16},
  year         = {2016},
}