Exploring CD79b, LC3, and TERT expression in NON-GCB DLBCL: markers associated with Rituximab-Cyclophosphamide-Doxorubicin-Vincristin-Prednisone treatment response

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma. The non-germinal center B-cell-like (non-GCB) subtype is associated with a poor prognosis and reduced response rates to rituximab cyclophosphamide-doxorubicin-vincristin-prednisone (R-CHOP) therapy. Resistance may involve cluster of differentiation 79B (CD79B)-driven B-cell receptor (BCR)/nuclear factor kappa B activation, microtubule-associated protein 1 light chain 3 (LC3)-mediated autophagy, and telomerase reverse transcriptase (TERT)-related survival signaling. The interrelationships between these markers and their associations with therapeutic responses remain unclear. This study evaluated the association between CD79B, LC3, and TERT expression and response to R-CHOP in non-GCB DLBCL. METHODS: This analytical case-control study included 58 paraffin-embedded samples from patients with non-GCB DLBCL diagnosed at the Dr. Hasan Sadikin General Hospital, Bandung, Indonesia (2017-2023). Tumor characteristics were assessed using immunohistochemical staining for CD79B, LC3, and TERT. Expression levels were evaluated semi-quantitatively based on staining intensity and the proportion of positive tumor cells. Treatment responses were categorized as response (complete/partial) or non-response (stable/progressive). Statistical analyses were performed using the chi-square test, Fisher's exact test, and binary logistic regression, with significance defined as p < 0.05. RESULTS: TERT, CD79B, and LC3 expression was detected in 53.4%, 55.2%, and 62.1% of the cases, respectively. Among non-responsive patients, TERT and LC3 expression rates were 62.1% and 69.0% (p > 0.05), respectively. CD79B expression was significantly associated with non-response (p = 0.002). Moreover, multivariate analysis identified positive CD79B expression as an independent predictor of non-response to R-CHOP therapy (OR = 9.72). CONCLUSION: CD79B expression was independently associated with a poor response to R-CHOP therapy in non-GCB DLBCL. The positive association between TERT and LC3 suggests the presence of additional metabolic adaptation mechanisms supporting tumor survival.