Identification and validation of a two-gene expression index for subtype classification and prognosis in Diffuse Large B-Cell Lymphoma.
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.
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.
Qinghua
Q
Xu
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.
Cong
C
Tan
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.
Shujuan
S
Ni
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.
Qifeng
Q
Wang
1] Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Shanghai, China [2] bioMérieux (Shanghai) Company Limited, Shanghai, China.
Fei
F
Wu
Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Shanghai, China.
Fang
F
Liu
1] Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Shanghai, China [2] bioMérieux (Shanghai) Company Limited, Shanghai, China.
Xun
X
Ye
1] Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Shanghai, China [2] bioMérieux (Shanghai) Company Limited, Shanghai, China.
Xia
X
Meng
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.
Weiqi
W
Sheng
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.
Xiang
X
Du
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D015534:Trans-Activators / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C403807:LIMD1 protein, human; C088831:MYBL1 protein, human; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators