Open AccessHuman endoplasmic reticulum oxidoreductin 1‐α is a novel predictor for poor prognosis of breast cancer
Author(s) -
Kutomi Goro,
Tamura Yasuaki,
Tanaka Tsutomu,
Kajiwara Toshimitsu,
Kukita Kazuharu,
Ohmura Tousei,
Shima Hiroaki,
Takamaru Tomoko,
Satomi Fukino,
Suzuki Yasuyo,
Torigoe Toshihiko,
Sato Noriyuki,
Hirata Koichi
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12177
Subject(s) - hero , breast cancer , endoplasmic reticulum , medicine , metastasis , cancer , univariate analysis , cancer research , oncology , pathology , biology , multivariate analysis , microbiology and biotechnology , artificial intelligence , computer science
Human endoplasmic reticulum oxidoreductin 1‐α ( hERO 1‐α) is an oxidizing enzyme that exists in the endoplasmic reticulum and its expression is augmented under hypoxia. It regulates a redox state of various kinds of protein through reoxidation of “client” protein disulfide isomerase. Interestingly, although the expression of hERO 1‐α in normal tissues was comparatively limited, various types of cancer cells expressed it in large amounts. Therefore, we examined the role of ERO1‐α in tumor growth using murine breast cancer line 4T1 and found that knockdown of murine ERO1‐α inhibited in vivo tumor growth and decreased lung metastasis compared with wild‐type 4T1. Moreover, we investigated the relationship between expression of hERO 1‐α and prognosis in breast cancer patients. Seventy‐one patients with breast cancer who underwent surgery between 2005 and 2006 in Sapporo Medical University Hospital (Sapporo, Japan) were analyzed in this study. Significant differences were found between the hERO 1‐α‐positive group ( n = 33) and hERO 1‐α‐negative group ( n = 38) in nuclear grade ( P < 0.001) and intrinsic subtype ( P = 0.021) in univariate analysis. More importantly, in multivariate analysis of disease‐free survival by Cox regression, expression of hERO 1‐α was the only independent prognosis factor ( P = 0.035). Finally, in univariate survival analysis, patients positive for hERO 1‐α had significantly shorter disease‐free survival and overall survival than those patients negative for hERO 1‐α. These findings indicate that the expression of hERO 1‐α in cancer cells is associated with poorer prognosis and thus can be a prognostic factor for patients with breast cancer.