Yokoyama Maki, Ichinoe Masaaki, Okina Sosei, Sakurai Yasutaka, Nakada Norihiro, Yanagisawa Nobuyuki, Jiang Shi-Xu, Numata Yoshiko, Umezawa Atsuko, Miyazaki Koji, Higashihara Masaaki, Murakumo Yoshiki
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
Int J Hematol. 2017 May;105(5):614-622. doi: 10.1007/s12185-016-2173-1. Epub 2016 Dec 28.
CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that negatively regulates TGF-β signaling. CD109 was originally identified in hematopoietic tumors; however, the significance of CD109 in hematopoietic malignancies remains unclear. Here, we study the association of CD109 with diffuse large B-cell lymphoma (DLBCL) prognosis. Eighty-four DLBCL specimens were immunohistochemically analyzed for CD109 expression, and 31 and 53 cases were classified into low- and high-CD109 expression groups, respectively. CD109 expression was not associated with overall survival using the Kaplan-Meier analysis and log-rank tests (P = 0.17); however, a significant association was observed between high-CD109 expression and low-1-year survival (P = 0.01). Moreover, in combination with the revised International Prognostic Index (R-IPI), R-IPI-poor/CD109-high was associated with poorer prognosis compared with R-IPI-poor alone. We assessed TGF-β signaling in CD109-depleted Nalm6 cells (a human B-lymphoblastic leukemia/lymphoma cell line), and found prolonged Smad2 phosphorylation compared with control cells after TGF-β1 stimulation, suggesting that CD109 attenuates TGF-β1 signaling in human B-cell tumors. These results suggest that CD109 is a putative biomarker for identifying a high-risk group among DLBCL patients.
CD109是一种糖基磷脂酰肌醇锚定糖蛋白，可负向调节转化生长因子-β（TGF-β）信号传导。CD109最初是在造血系统肿瘤中被鉴定出来的；然而，CD109在造血系统恶性肿瘤中的意义仍不明确。在此，我们研究CD109与弥漫性大B细胞淋巴瘤（DLBCL）预后的关系。对84例DLBCL标本进行CD109表达的免疫组织化学分析，分别将31例和53例分为低CD109表达组和高CD109表达组。使用Kaplan-Meier分析和对数秩检验，CD109表达与总生存期无关（P = 0.17）；然而，观察到高CD109表达与低1年生存率之间存在显著关联（P = 0.01）。此外，与修订后的国际预后指数（R-IPI）相结合，与单纯R-IPI不良相比，R-IPI不良/CD109高与更差的预后相关。我们评估了CD109缺失的Nalm6细胞（一种人B淋巴细胞白血病/淋巴瘤细胞系）中的TGF-β信号传导，发现在TGF-β1刺激后，与对照细胞相比，Smad2磷酸化延长，这表明CD109减弱了人B细胞肿瘤中的TGF-β1信号传导。这些结果表明，CD109是用于识别DLBCL患者中高危组的一种潜在生物标志物。
