A Bruton tyrosine kinase inhibitor-resistance gene signature predicts prognosis and identifies TRIP13 as a potential therapeutic target in diffuse large B-cell lymphoma.
Sci Rep
; 14(1): 21184, 2024 09 11.
Article
en En
| MEDLINE
| ID: mdl-39261532
ABSTRACT
Bruton tyrosine kinase inhibitor (BTKi)â¯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/ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma de Células B Grandes Difuso
/
Resistencia a Antineoplásicos
/
Agammaglobulinemia Tirosina Quinasa
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido