Harada Koji, Takenawa Takanori, Ferdous Tarannum, Kuramitsu Yasuhiro, Ueyama Yoshiya
Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Oncol Lett. 2017 Jun;13(6):4857-4862. doi: 10.3892/ol.2017.6062. Epub 2017 Apr 20.
We focused on the expression of Calreticulin (CALR) in oral squamous cell carcinoma (OSCC) on the basis of proteomic differential display analysis data. We used QR-32 cells in this study which is a regressive murine fibrosarcoma cell clone; and QRsP-11, a progressive malignant tumor cell clone originated from QR-32. CALR is an endoplasmic reticulum luminal Ca-binding chaperone protein, which is thought to affect the tumor behavior of various malignancies. This study was aimed to determine the usefulness of CALR as a prognostic factor in patients with OSCC. We investigated the expression of CALR in tissue samples taken from 111 OSCC patients by immunohistochemistry, and we also analyzed the relationship between CALR expression and patients' clinicopathological characteristics as well as patient survival. Positive immunohistchemical staining of CALR was observed in the cancer cell cytoplasm. Among 111 patients, high expression of CALR was observed in 44 patients (39.6%), whereas low expression was observed in 67 patients (60.4%). Significant association was found between CALR expression and T classification (P=0.0027), N classification (P=0.0219), stage (P=0.0013), and patient outcome (P=0.0014). Log-rank test showed that, there is a significant difference (P<0.0001) in 5-year survival rates between patients showing CALR high-expression (59.1%) and CALR low-expression (86.6%). According to our Multivariate analysis, reduced term survival of patients was correlated to high levels of CALR expression (P<0.0001). Our findings suggest that elevated expression of CALR might play an important role in tumor progression in OSCC, and could be considered as a useful prognostic factor in OSCC patients.
基于蛋白质组差异显示分析数据,我们聚焦于钙网蛋白(CALR)在口腔鳞状细胞癌(OSCC)中的表达。本研究使用了QR - 32细胞,它是一种退行性小鼠纤维肉瘤细胞克隆;以及QRsP - 11,一种源自QR - 32的进行性恶性肿瘤细胞克隆。CALR是一种内质网腔钙结合伴侣蛋白,被认为会影响各种恶性肿瘤的肿瘤行为。本研究旨在确定CALR作为OSCC患者预后因素的实用性。我们通过免疫组织化学研究了111例OSCC患者组织样本中CALR的表达情况,还分析了CALR表达与患者临床病理特征以及患者生存率之间的关系。在癌细胞胞质中观察到CALR免疫组织化学染色呈阳性。在111例患者中,44例(39.6%)观察到CALR高表达,而67例(60.4%)观察到低表达。发现CALR表达与T分期(P = 0.0027)、N分期(P = 0.0219)、阶段(P = 0.0013)和患者预后(P = 0.0014)之间存在显著关联。对数秩检验显示,CALR高表达患者(59.1%)和CALR低表达患者(86.6%)的5年生存率存在显著差异(P < 0.0001)。根据我们的多变量分析,患者生存期缩短与CALR高表达水平相关(P < 0.0001)。我们的研究结果表明,CALR表达升高可能在OSCC肿瘤进展中起重要作用,并且可被视为OSCC患者有用的预后因素。