LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients.
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.
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul, Republic of Korea.
Sung Gwe
SG
Ahn
Seung Myung
SM
Dong
Akira
A
Oshima
Woo Ho
WH
Kim
Hak Min
HM
Lee
Seung Ah
SA
Lee
Seung-Hyun
SH
Kwon
Ji-Hae
JH
Lee
Jae Myun
JM
Lee
Joon
J
Jeong
Hy-De
HD
Lee
Jeffrey E
JE
Green
D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002278:Carcinoma in Situ / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen; D018572:Disease-Free Survival; D004338:Drug Combinations; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D007797:Laminin; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003557:Phyllodes Tumor / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011509:Proteoglycans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology
D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human