Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

October 20, 2015

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Publicated to:Blood. 123 (19): 2915-2923 - 2014-05-08 123(19), DOI: 10.1182/blood-2013-11-536359

Authors: Iqbal, Javeed; Wright, George; Wang, Chao; Rosenwald, Andreas; Gascoyne, Randy D; Weisenburger, Dennis D; Greiner, Timothy C; Smith, Lynette; Guo, Shuangping; Wilcox, Ryan A; Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong; Rimsza, Lisa M; Jaffe, Elaine S; Campo, Elias; Martinez, Antonio; Delabie, Jan; Braziel, Rita M; Cook, James R; Tubbs, Raymond R; Ott, German; Geissinger, Eva; Gaulard, Philippe; Piccaluga, Pier Paolo; Pileri, Stefano A; Au, Wing Y; Nakamura, Shigeo; Seto, Masao; Berger, Francoise; de Leval, Laurence; Connors, Joseph M; Armitage, James; Vose, Julie; Chan, Wing C; Staudt, Louis M

Affiliations

Aichi Canc Ctr, Nagoya, Aichi 464, Japan - Author

Aichi Cancer Center, Nagoya, Japan - Author

British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada - Author

Centre for Lymphoid Cancer, British Columbia Cancer Agency, Centre for Lymphoid Cancers, Vancouver, BC, Canada - Author

Centre Hospitalier Lyon-Sud, Lyon, France - Author

CHU Vaudois, Univ Inst Pathol, CH-1011 Lausanne, Switzerland - Author

City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA - Author

Cleveland Clin, Dept Mol Pathol & Lab Med, Cleveland, OH 44106 USA - Author

Ctr Hosp Lyon Sud, Lyon, France - Author

Département de Pathologie, Institut National de la Santé et de la Recherche Médicale U955, Université Paris Est, Créteil, France - Author

Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States - Author

Department of Clinical Pathology, Oregon Health and Science University, Portland, OR, United States - Author

Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany - Author

Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, United States - Author

Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States - Author

Department of Molecular Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, United States - Author

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States - Author

Department of Pathology, City of Hope National Medical Center, Duarte, CA, United States - Author

Department of Pathology, Norwegian Radium Hospital, University of Oslo, Oslo, Norway - Author

Department of Pathology, University of Arizona, Tucson, AZ, United States - Author

Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany - Author

Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore - Author

Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain - Author

Institute of Hematology and Medical Oncology L. and A. Seràgnoli, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy - Author

Institute of Pathology, University of Würzburg, Würzburg, Germany - Author

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States - Author

Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States - Author

National Cancer Center, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore - Author

Natl Canc Ctr, Singapore, Singapore - Author

NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA - Author

NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA - Author

Oregon Hlth & Sci Univ, Dept Clin Pathol, Portland, OR 97201 USA - Author

Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China - Author

Queen Mary Hospital, Hong Kong, Hong Kong - Author

Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany - Author

Univ Arizona, Dept Pathol, Tucson, AZ USA - Author

Univ Barcelona, Hosp Clin, Inst Invest Bomed August Pi & Sunyer, Barcelona, Spain - Author

Univ Bologna, S Orsola Malpighi Hosp, Inst Hematol & Med Oncol L&A Seragnoli, Bologna, Italy - Author

Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA - Author

Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA - Author

Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA - Author

Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA - Author

Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway - Author

Univ Paris Est, Grp Henri Mondor Albert Chenevier, INSERM, Dept Pathol,U955, Creteil, France - Author

Univ Wurzburg, Inst Pathol, Wurzburg, Germany - Author

University Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland - Author

Abstract

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

Keywords

differentiationeffectorfeaturesidentificationpredictionprofilesrecognitionsubtypessurvivalAdultAgedAged, 80 and overAnaplastic lymphoma kinaseAngioimmunoblastic t cell lymphomaArticleCancer prognosisCancer survivalChemokine receptor cxcr3ClassificationControlled studyDendritic cellsDna microarrayFemaleGamma interferonGene expressionGene expression profilingGene expression regulationGene expression regulation, neoplasticGenetic associationGeneticsHumanHuman tissueHumansImmunohistochemistryImmunophenotypingInterleukin 18 receptor alphaInterleukin 2 receptor betaLarge cell lymphomaLymphoma, t-cell, peripheralMacrophage inflammatory protein 1alphaMajor clinical studyMaleMessenger rnaMetabolismMiddle agedMolecular diagnosisMonocyte chemotactic protein 1Myc proteinNk t cell lymphomaNotch1 receptorOligonucleotide array sequence analysisOverall survivalPeripheral t cell lymphomaPriority journalPrognosisProtein expressionStromal cell derived factor 1SurvivalSurvival analysisT cell leukemiaT cell lymphomaTranscription factor gata 3Transcription factor t betTumor markerTumor markers, biologicalTumor microenvironmentVery elderlyYoung adult

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Blood due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2014, it was in position 2/68, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.

This publication has been distinguished as a “Highly Cited Paper” by the agencies WoS (ESI, Clarivate) and ESI (Clarivate), meaning that it ranks within the top 1% of the most cited articles in its thematic field during the year of its publication. In terms of the observed impact of the contribution, this work is considered one of the most influential worldwide, as it is recognized as highly cited. (source consulted: ESI Nov 14, 2024)

And this is evidenced by the extremely high normalized impacts through some of the main indicators of this type, which, although dynamic over time and dependent on the set of average global citations at the time of calculation, already indicate that they are well above the average in different agencies:

Normalization of citations relative to the expected citation rate (ESI) by the Clarivate agency: 9.97 (source consulted: ESI Nov 14, 2024)
Weighted Average of Normalized Impact by the Scopus agency: 6.26 (source consulted: FECYT Feb 2024)
Field Citation Ratio (FCR) from Dimensions: 100.75 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-05, the following number of citations:

WoS: 382
Scopus: 253
Europe PMC: 259

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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Canada; China; France; Germany; Hong Kong; Italy; Japan; Norway; Singapore; Switzerland; United States of America.

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