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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Amino Acid Oxidoreductases / analysis*
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Amino Acid Oxidoreductases / biosynthesis
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Amino Acid Oxidoreductases / genetics
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Breast Neoplasms / chemistry*
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Breast Neoplasms / genetics
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Breast Neoplasms / mortality
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Breast Neoplasms / pathology
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Carcinoma / chemistry*
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Carcinoma / genetics
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Carcinoma / mortality
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Carcinoma / pathology
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Carcinoma in Situ / chemistry
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Carcinoma in Situ / genetics
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Carcinoma in Situ / mortality
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Carcinoma in Situ / pathology
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Cell Line, Tumor
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Cell Movement
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Collagen
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Disease-Free Survival
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Drug Combinations
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Epithelial-Mesenchymal Transition
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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In Situ Hybridization
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Kaplan-Meier Estimate
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Laminin
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Middle Aged
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Neoadjuvant Therapy
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Neoplasm Proteins / analysis*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasms, Multiple Primary / chemistry
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Neoplasms, Multiple Primary / genetics
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Neoplasms, Multiple Primary / mortality
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Neoplasms, Multiple Primary / pathology
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Phyllodes Tumor / chemistry
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Phyllodes Tumor / genetics
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Phyllodes Tumor / mortality
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Phyllodes Tumor / pathology
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Prognosis
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Proportional Hazards Models
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Proteoglycans
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RNA Interference
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RNA, Small Interfering / pharmacology
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Survival Analysis
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Tissue Array Analysis
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Triple Negative Breast Neoplasms / chemistry
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Triple Negative Breast Neoplasms / genetics
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Triple Negative Breast Neoplasms / mortality
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Triple Negative Breast Neoplasms / pathology
Substances
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Drug Combinations
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Laminin
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Neoplasm Proteins
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Proteoglycans
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RNA, Small Interfering
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matrigel
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Collagen
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Amino Acid Oxidoreductases
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LOXL2 protein, human