Xu Qinghua, Tan Cong, Ni Shujuan, Wang Qifeng, Wu Fei, Liu Fang, Ye Xun, Meng Xia, Sheng Weiqi, Du Xiang
1] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [2] Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China [3] Institute of Pathology, Fudan University, Shanghai, China [4] Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Shanghai, China [5] bioMérieux (Shanghai) Company Limited, Shanghai, China.
1] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [2] Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China [3] Institute of Pathology, Fudan University, Shanghai, China.
Sci Rep. 2015 May 5;5:10006. doi: 10.1038/srep10006.
The division of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes based on gene expression profiling has proved to be a landmark in understanding the pathogenesis of the disease. This study aims to identify a novel biomarker to facilitate the translation of research into clinical practice. Using a training set of 350 patients, we identified a two-gene expression signature, "LIMD1-MYBL1 Index", which is significantly associated with cell-of-origin subtypes and clinical outcome. This two-gene index was further validated in two additional dataset. Tested against the gold standard method, the LIMD1-MYBL1 Index achieved 81% sensitivity, 89% specificity for ABC group and 81% sensitivity, 87% specificity for GCB group. The ABC group had significantly worse overall survival than the GCB group (hazard ratio = 3.5, P = 0.01). Furthermore, the performance of LIMD1-MYBL1 Index was satisfactory compared with common immunohistochemical algorithms. Thus, the LIMD1-MYBL1 Index had considerable clinical value for DLBCL subtype classification and prognosis. Our results might prompt the further development of this two-gene index to a simple assay amenable to routine clinical practice.
基于基因表达谱将弥漫性大B细胞淋巴瘤（DLBCL）分为生发中心B细胞样（GCB）和活化B细胞样（ABC）亚型已被证明是理解该疾病发病机制的一个里程碑。本研究旨在确定一种新型生物标志物，以促进研究成果转化为临床实践。我们使用一个包含350例患者的训练集，确定了一个双基因表达特征，即“LIMD1-MYBL1指数”，它与起源细胞亚型及临床结局显著相关。该双基因指数在另外两个数据集中得到了进一步验证。与金标准方法相比，LIMD1-MYBL1指数对ABC组的敏感性为81%，特异性为89%；对GCB组的敏感性为81%，特异性为87%。ABC组的总生存期明显比GCB组差（风险比=3.5，P=0.01）。此外，与常见的免疫组化算法相比，LIMD1-MYBL1指数的表现令人满意。因此，LIMD1-MYBL1指数在DLBCL亚型分类和预后方面具有相当大的临床价值。我们的结果可能会促使将这个双基因指数进一步开发成一种适用于常规临床实践的简单检测方法。
