caArray_golub-00095: Diffuse large B-cell lymphoma outcome prediction

Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention. golub-00095 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Lymphoid tissue Material Types: synthetic_DNA, synthetic_RNA, organism_part Cell Types: B-Lymphocyte Disease States: Diffuse large B-cell Lymphoma, Follicular Lymphoma

弥漫性大B细胞淋巴瘤（Diffuse large B-cell lymphoma, DLBCL）是成人最常见的淋巴系统恶性肿瘤，仅不到50%的患者可获得临床治愈。目前临床上基于治疗前特征的预后模型，如国际预后指数（International Prognostic Index, IPI），被广泛用于预测DLBCL患者的临床转归。然而，这类临床预后模型既无法阐明临床异质性的分子基础，也无法识别特异性治疗靶点。本研究对接受环磷酰胺（cyclophosphamide）、阿霉素（adriamycin）、长春新碱（vincristine）与泼尼松（prednisone）联合（CHOP）方案化疗的DLBCL患者的诊断性肿瘤标本中6817个基因的表达水平进行了分析，并应用监督学习（supervised learning）预测方法区分治愈病例与致命或难治性病例。该算法将患者划分为两类，二者的5年总生存率（five-year overall survival rates）差异显著（70% vs 12%）。该模型还可有效区分特定IPI风险分层中有望治愈或死于疾病的患者。与DLBCL临床转归相关的基因包括若干调控B细胞受体（B-cell-receptor）信号通路应答、关键丝氨酸/苏氨酸磷酸化通路（serine/threonine phosphorylation pathways）及细胞凋亡（apoptosis）的基因。本研究结果表明，监督学习分类技术可有效预测DLBCL的临床转归，并识别合理的干预靶点。
golub-00095
检测类型：基因表达
提供商：Affymetrix
阵列设计：Hu6800
物种：智人（NCBI分类号）
组织部位：淋巴组织
材料类型：合成DNA、合成RNA、生物体组织
细胞类型：B淋巴细胞
疾病状态：弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤