Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context
Summary: 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 i...
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2025-05-01
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| author | Yu-Jia Huo Shu Cheng Hong-Mei Yi Ting Niu Lei Fan Guo-Hui Cui Fu-Ling Zhou Xian-Min Song Fei Li Ou Bai Xiao-Jing Yan Jun Shi Ming-Ci Cai Yao-Hui Huang Lei Dong Jie Xiong Song Hu Yu-Ran Qiu Yan Zhao Peng-Peng Xu Li Wang Min Lu Hong-Mei Jing Wei-Li Zhao |
| author_facet | Yu-Jia Huo Shu Cheng Hong-Mei Yi Ting Niu Lei Fan Guo-Hui Cui Fu-Ling Zhou Xian-Min Song Fei Li Ou Bai Xiao-Jing Yan Jun Shi Ming-Ci Cai Yao-Hui Huang Lei Dong Jie Xiong Song Hu Yu-Ran Qiu Yan Zhao Peng-Peng Xu Li Wang Min Lu Hong-Mei Jing Wei-Li Zhao |
| author_sort | Yu-Jia Huo |
| collection | DOAJ |
| description | Summary: 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. Funding: This study was supported by National Key R&D Program of China, National Natural Science Foundation of China, Clinical Research Plan of Shanghai Hospital Development Centre, Shanghai Clinical Research Centre for Cell Therapy, Shanghai Municipal Health Commission, and China Postdoctoral Science Foundation. |
| format | Article |
| id | doaj-art-a633968eb9a146a5ba8243d8d02aed3f |
| institution | OA Journals |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| spelling | doaj-art-a633968eb9a146a5ba8243d8d02aed3f2025-08-20T02:09:26ZengElsevierEBioMedicine2352-39642025-05-0111510569310.1016/j.ebiom.2025.105693Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in contextYu-Jia Huo0Shu Cheng1Hong-Mei Yi2Ting Niu3Lei Fan4Guo-Hui Cui5Fu-Ling Zhou6Xian-Min Song7Fei Li8Ou Bai9Xiao-Jing Yan10Jun Shi11Ming-Ci Cai12Yao-Hui Huang13Lei Dong14Jie Xiong15Song Hu16Yu-Ran Qiu17Yan Zhao18Peng-Peng Xu19Li Wang20Min Lu21Hong-Mei Jing22Wei-Li Zhao23Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Hematology, First Hospital of Jilin University, Jilin, ChinaDepartment of Hematology, First Hospital of China Medical University, Shenyang, ChinaDepartment of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China; Corresponding author. Department of Hematology, Lymphoma Research Centre, Peking University Third Hospital, Beijing, 100191, China.Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China; Corresponding author. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.Summary: 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. Funding: This study was supported by National Key R&D Program of China, National Natural Science Foundation of China, Clinical Research Plan of Shanghai Hospital Development Centre, Shanghai Clinical Research Centre for Cell Therapy, Shanghai Municipal Health Commission, and China Postdoctoral Science Foundation.http://www.sciencedirect.com/science/article/pii/S2352396425001379Peripheral T-cell lymphomaCD30Molecular subtypeMicroenvironmentTargeted therapyBrentuximab vedotin |
| spellingShingle | Yu-Jia Huo Shu Cheng Hong-Mei Yi Ting Niu Lei Fan Guo-Hui Cui Fu-Ling Zhou Xian-Min Song Fei Li Ou Bai Xiao-Jing Yan Jun Shi Ming-Ci Cai Yao-Hui Huang Lei Dong Jie Xiong Song Hu Yu-Ran Qiu Yan Zhao Peng-Peng Xu Li Wang Min Lu Hong-Mei Jing Wei-Li Zhao Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context EBioMedicine Peripheral T-cell lymphoma CD30 Molecular subtype Microenvironment Targeted therapy Brentuximab vedotin |
| title | Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context |
| title_full | Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context |
| title_fullStr | Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context |
| title_full_unstemmed | Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context |
| title_short | Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre studyResearch in context |
| title_sort | molecular heterogeneity of cd30 peripheral t cell lymphoma with prognostic significance and therapeutic implications a retrospective multi centre studyresearch in context |
| topic | Peripheral T-cell lymphoma CD30 Molecular subtype Microenvironment Targeted therapy Brentuximab vedotin |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425001379 |
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