Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
Ann Hematol. 2014 Mar;93(3):437-47. doi: 10.1007/s00277-013-1884-0. Epub 2013 Aug 24.
We performed the whole genome cDNA-mediated annealing, selection and ligation assay with 164 formalin-fixed paraffin-embedded (FFPE) tumor samples to develop robust prognostic gene expression profiles in patients with diffuse large B cell lymphoma. The prognostic gene expression profiles were developed and validated by a gradient lasso and leave-one-out cross-validation process. We identified a set of genes whose expression provided prognostic indicators from whole data set (PRKCDBP, CASP10, FAM3C, KCNK12, MAN1A2, PRND, RAB1A, TMEM39B, SLC6A6, MMP12, FEM1B, C3orh37, RBP1, HK1, LOC400464, KIAA0746, and SLC25A23). This gene expression profile-based risk model could classify patients into two cross-validated risk groups with a significant difference in 5-year progression-free survival rates (71.1 vs. 45.5 %) and with a hazard ratio for recurrence of 2.45 (95 % CI, 1.44-4.16, P = 0.001). This model provided prognostic information independent of the International Prognostic Index (IPI), and discriminated high-risk group from patients belong to high/high-intermediate risk of IPI and activated B cell-like type. Thus, gene expression profiling from FFPE could provide additional prognostic information for diffuse large B cell lymphoma and our data underscore the need for development of risk-adapted treatment strategies based on gene expression profiles.
我们对 164 例福尔马林固定石蜡包埋（FFPE）肿瘤样本进行了全基因组 cDNA 介导的退火、选择和连接分析，以开发弥漫性大 B 细胞淋巴瘤患者稳健的预后基因表达谱。通过梯度lasso 和留一法交叉验证过程开发和验证了预后基因表达谱。我们确定了一组基因，其表达可提供来自全数据集的预后指标（PRKCDBP、CASP10、FAM3C、KCNK12、MAN1A2、PRND、RAB1A、TMEM39B、SLC6A6、MMP12、FEM1B、C3orh37、RBP1、HK1、LOC400464、KIAA0746 和 SLC25A23）。这种基于基因表达谱的风险模型可以将患者分为两个交叉验证的风险组，5 年无进展生存率有显著差异（71.1%对 45.5%），复发风险比为 2.45（95%CI，1.44-4.16，P=0.001）。该模型提供了独立于国际预后指数（IPI）的预后信息，并将高危组与属于 IPI 高/高中危和激活 B 细胞样型的患者区分开来。因此，FFPE 的基因表达谱分析可为弥漫性大 B 细胞淋巴瘤提供额外的预后信息，我们的数据强调需要根据基因表达谱制定风险适应的治疗策略。
