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Identification and Validation of a Two-gene Expression Index for Subtype Classification and Prognosis in Diffuse Large B-Cell Lymphoma

Overview
Journal Sci Rep
Specialty Science
Date 2015 May 6
PMID 25940947
Citations 11
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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.

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References
1.
Kiss H, Kedra D, Yang Y, Kost-Alimova M, Kiss C, OBrien K . A novel gene containing LIM domains (LIMD1) is located within the common eliminated region 1 (C3CER1) in 3p21.3. Hum Genet. 2000; 105(6):552-9. DOI: 10.1007/s004399900188. View

2.
Scott D, Wright G, Williams P, Lih C, Walsh W, Jaffe E . Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood. 2014; 123(8):1214-7. PMC: 3931191. DOI: 10.1182/blood-2013-11-536433. View

3.
Heckman C, Mehew J, Ying G, Introna M, Golay J, Boxer L . A-Myb up-regulates Bcl-2 through a Cdx binding site in t(14;18) lymphoma cells. J Biol Chem. 2000; 275(9):6499-508. DOI: 10.1074/jbc.275.9.6499. View

4.
Arsura M, Hofmann C, Golay J, Introna M, Sonenshein G . A-myb rescues murine B-cell lymphomas from IgM-receptor-mediated apoptosis through c-myc transcriptional regulation. Blood. 2000; 96(3):1013-20. View

5.
Rosenwald A, Wright G, Chan W, Connors J, Campo E, Fisher R . The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346(25):1937-47. DOI: 10.1056/NEJMoa012914. View