Malumbres Raquel, Chen Jun, Tibshirani Rob, Johnson Nathalie A, Sehn Laurie H, Natkunam Yaso, Briones Javier, Advani Ranjana, Connors Joseph M, Byrne Gerald E, Levy Ronald, Gascoyne Randy D, Lossos Izidore S
Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA.
Blood. 2008 Jun 15;111(12):5509-14. doi: 10.1182/blood-2008-02-136374. Epub 2008 Apr 29.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies. However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP-treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS; P = .002) and progression-free survival (PFS; P = .038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (P = .002 and .010, respectively) and was independent of the IPI for prediction of OS (P = .008). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.
弥漫性大B细胞淋巴瘤（DLBCL）是一种异质性疾病，临床结局各异。诊断时的结局预测至关重要。此前，我们构建了一个6基因模型，用于预测接受蒽环类化疗的DLBCL患者的结局。然而，标准治疗已演变为利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松（R-CHOP）。在此，我们评估了基于石蜡的6基因模型对接受R-CHOP治疗的DLBCL患者的预测能力。成功从132份福尔马林固定石蜡包埋（FFPE）标本中提取了RNA。测量了构成该模型的6个基因的表达，并为每位患者计算了死亡预测评分。死亡预测评分将患者分为低风险（低于中位数）和高风险（高于中位数）亚组，其总生存期（OS；P = .002）和无进展生存期（PFS；P = .038）有显著差异。当将死亡预测评分视为连续变量时，该模型也能预测OS和PFS（分别为P = .002和.010），并且在预测OS时独立于国际预后指数（IPI；P = .008）。这些发现表明，在R-CHOP治疗时代，6基因模型的预后价值仍然显著，并且该模型可应用于初始诊断活检的常规FFPE组织。
