2. Academic Validation
  3. Reduced OTUD7B expression correlates with poor prognosis in PTCL via non-canonical NF-κB

Reduced OTUD7B expression correlates with poor prognosis in PTCL via non-canonical NF-κB

  • Int J Hematol. 2025 Feb;121(2):194-205. doi: 10.1007/s12185-024-03877-y.
Feng Chen # 1,  Shi Qiu # 1,  Ailing Gui # 1,  Shiyu Jiang 2,  Yichen Yan 1,  Jichuan Wu 3,  Guangliang Chen 2,  Shun Zhu 1,  Yizhen Liu 2,  Zuguang Xia 2,  Baohua Yu 4,  Xiaojian Sun 5,  Juan Jennifer Gu 6,  Lan Wang 3,  Wen Liu 1,  Ling Yang 1,  Qunling Zhang 2,  Ji Zuo 7
Affiliations

Affiliations

  • 1 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 2 Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 3 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 4 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 5 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.
  • 6 Department of Medicine & Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
  • 7 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. jzuo@shmu.edu.cn.
  • # Contributed equally.
PMID: 39636331 DOI: 10.1007/s12185-024-03877-y
Abstract

Peripheral T cell lymphoma (PTCL) is an aggressive and highly heterogeneous lymphoma with a bleak prognosis, highlighting the urgent need for an effective biomarker to guide therapeutic strategies. Ovarian tumor domain-containing 7B (OTUD7B) has been shown to have a critical function in the progression of cancers. However, the prognostic significance of OTUD7B in PTCL remains unexplored. In this study, we demonstrated for the first time that PTCL patients with low expression of OTUD7B had shorter progression-free survival (PFS) and overall survival (OS). In addition, OTUD7B knockdown promoted chemoresistance to doxorubicin in PTCL cell lines, and led to increased translocation of p52 from the cytoplasm to the nucleus. Inhibition of non-canonical NF-κB partially restored the sensitivity of PTCL cells to doxorubicin. Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

Keywords

Non-canonical NF-κB; OTUD7B; PTCL.

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