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作者

Zijun Y Xu-Monette, Li Wei, Xiaosheng Fang, Qingyan Au, Harry Nunns, Máté Nagy, Alexandar Tzankov, Feng Zhu, Carlo Visco, Govind Bhagat, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Xiaoping Sun, Xin Han, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, J Han van Krieken, Miguel A Piris, Jane N Winter, Yong Li, Bing Xu, Hua You, Maher Albitar, Ken H Young

作者单位

NeoGenomics Laboratories. Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University. n Jimé nez Dí Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute. Pathology, University of Basel, Hospital. Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University. Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital. 10 Department of Hematology, Aalborg University Hospital. 11 Pathology, MSKCC. 12 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine. 13 Pathology and Genomic Medicine, Houston Methodist Hospital. 14 Pathology, Wake Forest School of Medicine. 15 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center. 16 Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center. 17 The University of Texas MD Anderson Cancer Center. 18 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine. 19 Pathology, San Raffaele Scientific Institute. 20 Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute. 21 Department of Pathology, Odense University Hospital. 22 Gundersen Lutheran Health System. 23 Pathology, Radboud university medical centre. 24 Fundació az, Spain. 25 Department of Medicine, Feinberg School of Medicine, Northwestern University. 26 Medicine, Baylor College of Medicine. 27 Department of Heamatology, Southern Medical University. 28 Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou. 29 Hematology/Oncology, NeoGenomics Laboratories. 30 Pathology, Duke University School of Medicine ken.young@duke.edu. Duke University. NeoGenomics. Affiliations Department of Medicine, Section of Hematology, University of Verona.

刊名

Clinical cancer research : an official journal of the American Association for Cancer Research

年份

2022

ISSN

1078-0432

摘要

Purpose: Diffuse large B-cell lymphoma is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, B cell-of-origin or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double-expression is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL...更多

Purpose: Diffuse large B-cell lymphoma is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, B cell-of-origin or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double-expression is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers. Experimental design: We performed targeted next-generation sequencing, immunohistochemistry for MYC, BCL2, and FN1, and fluorescent multiplex immunohistochemistry for microenvironmental markers in a large cohort of DLBCL. We performed correlative and prognostic analyses within and across DLBCL genetic subtypes and MYC/BCL2 double-expressors. Results: We found that MYC/BCL2 double-high-expression had significant adverse prognostic impact within the EZB genetic subtype and LymphGen-unclassified DLBCL cases but not within MCD and ST2 genetic subtypes. Conversely, KMT2D mutations significantly stratified DhE but not non-DhE DLBCL. T-cell infiltration showed favorable prognostic effects within BN2, MCD, and DhE but unfavorable within ST2 and LymphGen-unclassified cases. FN1 and PD-1-high expression had significant adverse prognostic effects within multiple DLBCL genetic/phenotypic subgroups. The prognostic effects of DhE and immune biomarkers within DLBCL genetic subtypes were independent although DhE and high Ki-67 were significantly associated with lower T-cell infiltration in LymphGen-unclassified cases. Conclusions: Together, these results demonstrated independent and additive prognostic effects of phenotypic MYC/BCL2 and microenvironment biomarkers and genetic subtyping in DLBCL prognostication, important for improving DLBCL classification and identifying prognostic determinants and therapeutic targets.收起

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