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Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre study

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机构: [1]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai,Sch Med,State K, Shanghai 200025, Peoples R China [2]Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Sch Med, Dept Pathol, Shanghai, Peoples R China [3]Sichuan Univ, West China Hosp, Dept Hematol, Chengdu, Peoples R China [4]Nanjing Med Univ, Affiliated Hosp 1, Pukou CLL Ctr, Dept Hematol, Nanjing, Peoples R China [5]Huazhong Univ Sci & Technol, Union Hosp, Inst Hematol, Tongji Med Coll, Wuhan, Peoples R China [6]Wuhan Univ, Zhongnan Hosp, Dept Hematol, Wuhan, Peoples R China [7]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Hematol, Shanghai, Peoples R China [8]Nanchang Univ, Affiliated Hosp 1, Ctr Hematol, Nanchang, Peoples R China [9]First Hosp Jilin Univ, Dept Hematol, Jilin, Peoples R China [10]First Hosp China Med Univ, Dept Hematol, Shenyang, Peoples R China [11]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Hematol, Shanghai, Peoples R China [12]Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China [13]Pole Rech Sino Francais Sci Vivant & Genom, Lab Mol Pathol, Shanghai, Peoples R China [14]Peking Univ Third Hosp, Lymphoma Res Ctr, Dept Hematol, Beijing 100191, Peoples R China
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关键词: Peripheral T-cell lymphoma CD30 Molecular subtype Microenvironment Targeted therapy Brentuximab vedotin

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Background Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous group of non-Hodgkin's lymphomas, often with aggressive biological behaviour. CD30 serves as a pivotal surface antigen in PTCL, however, its biological functions and therapeutic potential warrant further investigation. Methods We analysed 415 de novo patients with PTCL including 314 in the training cohort and 101 in the validation cohort across 11 medical centres in China. Genomic and transcriptomic profiles were examined by DNA-and RNA-sequencing in 355 and 169 patients, respectively. Findings In both cohorts, CD30+ PTCL presented significantly increased frequencies of SETD2, STAT3, and PTPRS mutations. Therefore, three molecular subtypes with distinct biological signatures were identified, including the HMA subtype characterised by dysregulation of histone methylation and acetylation, the JNE subtype by alterations in JAK-STAT, Notch signalling pathway, and EBV infection, and the PCT subtype by mutations in phosphorylation, chromatin remodelling, and T-cell receptor-major histocompatibility complex interaction, with extracellular matrix enrichment. Clinically, the JNE subtype demonstrated inferior progression-free survival (PFS) and overall survival (OS), as compared to the HMA and PCT subtypes. Brentuximab vedotin (BV)-containing treatment was associated with improved PFS and OS in the JNE and PCT subtypes. Furthermore, gene expression profile analysis demonstrated underlying vulnerabilities for the HMA, JNE, and PCT subtypes to epigenome-targeting agents, JAK or PI3K inhibitors, and PD-1 inhibitors, respectively. Interpretation The molecular subtypes of CD30+ PTCL demonstrated prognostic significance and varied sensitivity to BV treatment. Our findings further elucidated molecular regulatory networks of CD30+ PTCL, providing potential co-targeted approaches for genotype-guided precision medicine in PTCL. Copyright (c) 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai,Sch Med,State K, Shanghai 200025, Peoples R China
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通讯机构: [1]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai,Sch Med,State K, Shanghai 200025, Peoples R China [13]Pole Rech Sino Francais Sci Vivant & Genom, Lab Mol Pathol, Shanghai, Peoples R China
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