Human endoplasmic reticulum oxidoreductin 1‐α is a novel predictor for poor prognosis of breast cancer

Cancer Science

Goro Kutomi¹  Yasuaki Tamura²  Tsutomu Tanaka²  Toshimitsu Kajiwara²  Kazuharu Kukita¹  Tousei Ohmura¹  Hiroaki Shima¹  Tomoko Takamaru¹  Fukino Satomi¹  Yasuyo Suzuki¹  Toshihiko Torigoe²  Noriyuki Sato² 

[1]Department of Surgery, Sapporo Medical University, School of Medicine, Sapporo, Japan

[2]Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan

DOI  :  10.1111/cas.12177

来源: Wiley

【 摘 要 】

Abstract

Human endoplasmic reticulum oxidoreductin 1-α (hERO1-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 hERO1-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 hERO1-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 hERO1-α-positive group (n = 33) and hERO1-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 hERO1-α was the only independent prognosis factor (P = 0.035). Finally, in univariate survival analysis, patients positive for hERO1-α had significantly shorter disease-free survival and overall survival than those patients negative for hERO1-α. These findings indicate that the expression of hERO1-α in cancer cells is associated with poorer prognosis and thus can be a prognostic factor for patients with breast cancer.

【 授权许可】

Unknown   
© 2013 Japanese Cancer Association