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Identification and validation of a two-gene expression index for subtype classification and prognosis in Diffuse
Qinghua Xu1, Cong Tan2, Shujuan Ni2
11] 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.
Abstract:
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.
