LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients

Sung Gwe Ahn, Seung Myung Dong, Akira Oshima, Woo Ho Kim, Hak Min Lee, Seung Ah Lee, Seung Hyun Kwon, Ji Hae Lee, Jae Myun Lee, Jeong Joon, Hy De Lee, Jeffrey E. Green

Research output: Contribution to journalArticle

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Abstract

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalBreast Cancer Research and Treatment
Volume141
Issue number1
DOIs
Publication statusPublished - 2013 Aug 1

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Protein-Lysine 6-Oxidase
Breast Neoplasms
Survival
Cell Line
Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Survival Analysis
Proportional Hazards Models
Estrogen Receptors
Wound Healing

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ahn, Sung Gwe ; Dong, Seung Myung ; Oshima, Akira ; Kim, Woo Ho ; Lee, Hak Min ; Lee, Seung Ah ; Kwon, Seung Hyun ; Lee, Ji Hae ; Lee, Jae Myun ; Joon, Jeong ; Lee, Hy De ; Green, Jeffrey E. / LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients. In: Breast Cancer Research and Treatment. 2013 ; Vol. 141, No. 1. pp. 89-99.
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abstract = "Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 {\%} of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 {\%}, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 {\%}; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.",
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Ahn, SG, Dong, SM, Oshima, A, Kim, WH, Lee, HM, Lee, SA, Kwon, SH, Lee, JH, Lee, JM, Joon, J, Lee, HD & Green, JE 2013, 'LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients', Breast Cancer Research and Treatment, vol. 141, no. 1, pp. 89-99. https://doi.org/10.1007/s10549-013-2662-3

LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients. / Ahn, Sung Gwe; Dong, Seung Myung; Oshima, Akira; Kim, Woo Ho; Lee, Hak Min; Lee, Seung Ah; Kwon, Seung Hyun; Lee, Ji Hae; Lee, Jae Myun; Joon, Jeong; Lee, Hy De; Green, Jeffrey E.

In: Breast Cancer Research and Treatment, Vol. 141, No. 1, 01.08.2013, p. 89-99.

Research output: Contribution to journalArticle

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T1 - LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients

AU - Ahn, Sung Gwe

AU - Dong, Seung Myung

AU - Oshima, Akira

AU - Kim, Woo Ho

AU - Lee, Hak Min

AU - Lee, Seung Ah

AU - Kwon, Seung Hyun

AU - Lee, Ji Hae

AU - Lee, Jae Myun

AU - Joon, Jeong

AU - Lee, Hy De

AU - Green, Jeffrey E.

PY - 2013/8/1

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N2 - Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

AB - Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

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