Okina Sosei, Yanagisawa Nobuyuki, Yokoyama Maki, Sakurai Yasutaka, Numata Yoshiko, Umezawa Atsuko, 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. 2015 Dec;102(6):662-9. doi: 10.1007/s12185-015-1880-3. Epub 2015 Oct 8.
REV7 is a multifunctional protein involved in DNA damage tolerance, cell-cycle regulation, gene expression, and carcinogenesis. Although its expression is reportedly associated with poor prognosis in human solid tissue cancers, the significance of REV7 expression in hematopoietic malignancies is unclear. This study evaluated the prognostic significance of REV7 expression in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-combined chemotherapy. Using immunohistochemistry, we analyzed 83 specimens of de novo DLBCL [38 germinal center B-cell-like (GCB) and 45 non-GCB DLBCLs] treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone for REV7 expression. Aberrant REV7 expression was detected in DLBCL cell nuclei. High REV7 expression was associated with significantly shorter overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis and log-rank tests (P < 0.01 and P < 0.01, respectively). Multivariate analysis revealed that REV7 expression is an independent prognostic factor for both OS and PFS. Additionally, when patients were divided into four groups using a combination of REV7 expression and international prognostic index (IPI) or Bcl-2 expression, REV7(High)/IPI(Poor) and REV7(High)/Bcl-2(High) patients showed the poorest outcome. These results indicate that REV7 may be a useful biomarker to predict the prognosis of patients with DLBCL treated with rituximab.
REV7是一种多功能蛋白，参与DNA损伤耐受、细胞周期调控、基因表达和致癌过程。尽管据报道其表达与人类实体组织癌症的不良预后相关，但REV7在血液系统恶性肿瘤中的表达意义尚不清楚。本研究评估了REV7表达在接受利妥昔单抗联合化疗的弥漫性大B细胞淋巴瘤（DLBCL）患者中的预后意义。我们采用免疫组织化学方法，分析了83例接受利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松龙治疗的初治DLBCL标本（38例生发中心B细胞样（GCB）和45例非GCB DLBCL）中的REV7表达情况。在DLBCL细胞核中检测到异常的REV7表达。使用Kaplan-Meier分析和对数秩检验，高REV7表达与显著缩短的总生存期（OS）和无进展生存期（PFS）相关（分别为P < 0.01和P < 0.01）。多变量分析显示，REV7表达是OS和PFS的独立预后因素。此外，当根据REV7表达与国际预后指数（IPI）或Bcl-2表达的组合将患者分为四组时，REV7（高）/IPI（差）和REV7（高）/Bcl-2（高）的患者预后最差。这些结果表明，REV7可能是预测接受利妥昔单抗治疗的DLBCL患者预后的有用生物标志物。
