Watanabe Manabu, Shibata Masahiro, Inaishi Takahiro, Ichikawa Takahiro, Soeda Ikumi, Miyajima Noriyuki, Takano Yuko, Takeuchi Dai, Tsunoda Nobuyuki, Kanda Mitsuro, Kikumori Toyone, Kodera Yasuhiro, Nagino Masato
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Oncol Lett. 2020 Nov;20(5):198. doi: 10.3892/ol.2020.12059. Epub 2020 Sep 4.
Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker.
乳腺癌(BC)是女性中最常见的恶性肿瘤。新型生物标志物或治疗靶点的开发可能有助于改善患者的预后。边缘区B细胞和B1细胞特异性蛋白(MZB1)是一种与未折叠蛋白反应相关的伴侣蛋白,主要存在于B淋巴细胞的内质网中,尽管其在BC细胞中的作用尚不清楚。本研究旨在探讨MZB1表达在BC中的意义。首先,评估了13种BC细胞系和两种非癌性乳腺细胞系中的mRNA表达水平。接下来,评估了BC患者肿瘤标本中MZB1的mRNA和蛋白表达,以评估其表达与临床病理因素或预后之间的关联。在四种雌激素受体(ER)阳性的BC细胞系中可检测到mRNA表达水平。当评估BC与非癌标本之间的mRNA表达水平比值时,III期疾病患者的比值高于0/I/II期疾病患者(P=0.009)。使用免疫组织化学方法,与ER阴性的BC患者相比,ER阳性的BC患者更频繁地表达MZB1(P=0.003)。在ER阳性的BC患者中,MZB1阳性的BC患者的无病生存期(DFS)比阴性患者短(P=0.026)。DFS的多因素分析表明,MZB1阳性是一个独立的预后因素(P=0.022)。本研究结果表明,MZB1表达可能与BC的更晚期阶段相关。此外,在ER阳性的BC患者中,MZB1可能是一种潜在的预后标志物。