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- Title
A Bruton tyrosine kinase inhibitor-resistance gene signature predicts prognosis and identifies TRIP13 as a potential therapeutic target in diffuse large B-cell lymphoma.
- Authors
Ding, Yangyang; Huang, Keke; Sun, Cheng; Liu, Zelin; Zhu, Jinli; Jiao, Xunyi; Liao, Ya; Feng, Xiangjiang; Guo, Jingjing; Zhu, Chunhua; Zhai, Zhimin; Xiong, Shudao
- Abstract
Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL.
- Subjects
BRUTON tyrosine kinase; DIFFUSE large B-cell lymphomas; PROTEIN-tyrosine kinase inhibitors; PROGNOSIS; DRUG resistance
- Publication
Scientific Reports, 2024, Vol 14, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-024-72121-8