What question did this study set out to answer?

The study aims to explore how CD59 silencing affects doxorubicin sensitivity and prognosis in DLBCL patients.

April 3, 2026Clinical and Experimental Medicine0 citationsOpen Access

CD59 silencing enhances doxorubicin sensitivity in DLBCL cells and is associated with poor prognosis in patients treated with CHOP regimen

LLinzhu MXMaimaitirexiati Xianmusiya SWShujuan Wen

Key Points

The study aims to explore how CD59 silencing affects doxorubicin sensitivity and prognosis in DLBCL patients.
Lentiviral-mediated knockdown of CD59 in DLBCL cell lines
Assessment of cell viability, cell cycle, and apoptosis using CCK-8 and flow cytometry
Immunohistochemistry analysis of tumor biopsies from treatment-naive DLBCL patients
Survival analysis using Kaplan-Meier and Cox regression models
CD59 knockdown reduced cell viability and increased apoptosis in DLBCL cells
Combination of CD59 silencing with doxorubicin significantly enhanced treatment efficacy
High CD59 expression was linked to poorer prognosis in CHOP-treated patients
CD59 positivity correlates with higher IPI scores and elevated LDH levels

Abstract

Diffuse large B-cell lymphoma (DLBCL) remains challenging due to high relapse and refractory rates after R-CHOP therapy. The role of complement regulatory protein CD59 in DLBCL progression and drug resistance is poorly understood. This study aimed to investigate the effects of knocking-down complement-regulatory protein, CD59, on disease progression, and chemo-resistance in DLBCL cells, as well as to establish the clinicopathological relevance and prognostic significance of CD59 in DLBCL. Lentiviral-mediated knockdown of CD59 was established in SU-DHL-4 and U2932 DLBCL cell lines. Cell viability, cell cycle distribution, and apoptosis were assessed using CCK-8 and flow cytometry. Immunohistochemistry for CD59 was performed on tumor biopsies from 103 treatment-naive DLBCL patients. Survival analyses were conducted using Kaplan-Meier and Cox regression models. Stable silencing of CD59 significantly reduced cell viability, induced G₀/G₁ arrest, and promoted apoptosis in both cell lines. The combination with doxorubicin resulted in enhanced growth inhibition and apoptosis compared to monotherapy. In clinical samples, CD59 positivity (n = 43, 41.75%) was correlated with a higher IPI score (p < 0.05), elevated LDH (p < 0.05), and a poorer response to therapy (CHOP, p < 0.05). In CHOP-treated patients, CD59 + predicted shorter PFS (rate, 9.1% vs. 61.4%, p < 0.05) and OS (45.5% vs. 86.9%, p < 0.05), while no significant difference was observed in the R-CHOP subgroup. Multivariate analysis confirmed that CD59 overexpression was an independent predictor of poor PFS and OS (HR = 4.254, p < 0.05). CD59 knockdown suppresses DLBCL cell growth and enhances doxorubicin sensitivity in vitro. Clinically, the prognostic value of CD59 is highly treatment-regimen dependent: high CD59 expression is an independent predictor of poor prognosis specifically in CHOP-treated DLBCL patients, but not in those receiving the standard R-CHOP regimen. These findings highlight CD59 as a potential modulator of chemotherapy response rather than a broadly applicable biomarker.

问 AI

Bookmark

View Full Paper