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Published on: January 7, 2013
Prognostic impact of protein kinase C beta II expression in R-CHOP-treated diffuse large B-cell lymphoma patients
Sari Riihijärvi1, Satu Koivula, Heidi Nyman
1Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
Abstract:
Development of targeted agents for the treatment of diffuse large B-cell lymphoma includes clinical evaluation of enzastaurin, an agent that suppresses signaling through protein kinase C-beta and AKT pathways. To determine whether protein kinase C-beta expression has prognostic significance for diffuse large B-cell lymphoma patients treated with immunochemotherapy, we analyzed the expression of protein kinase C-beta II, BCL-2 and cell of origin immunohistochemically from pretreatment samples of 95 diffuse large B-cell lymphoma patients. All patients received rituximab with CHOP or CHOEP. According to Kaplan-Meier analyses, overall survival at 3 years was better among the patients with low than high protein kinase C-beta II protein levels (94 vs 76%, P=0.036). The prognostic value of protein kinase C-beta II expression on survival was seen in the patients with low and high International Prognostic Index risk groups, and in all molecular entities. Gene expression data from an independent set of 233 diffuse large B-cell lymphoma patients treated with a combination of rituximab and CHOP-like chemotherapy was analyzed in comparison. Accordingly, a better 3-year overall survival was observed among the subgroup with low protein kinase C-beta II mRNA levels (84 vs 68%, P=0.005). In multivariate analysis with cell of origin, protein kinase C-beta II mRNA expression remained as an independent predictor for overall survival. Together, the data show that protein kinase C-beta II expression has prognostic significance in diffuse large B-cell lymphoma patients treated with immunochemotherapy.
Insights
Low protein kinase C-beta II expression predicts better survival in diffuse large B-cell lymphoma (DLBCL) patients receiving immunochemotherapy. This finding holds across various risk groups and molecular subtypes, highlighting its prognostic value.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Diffuse large B-cell lymphoma (DLBCL) treatment involves targeted agents like enzastaurin, which affects protein kinase C-beta (PKCβ) and AKT pathways.
- Understanding prognostic markers is crucial for optimizing immunochemotherapy regimens in DLBCL.
Purpose of the Study:
- To investigate the prognostic significance of protein kinase C-beta II (PKCβII) expression in DLBCL patients treated with immunochemotherapy.
- To correlate PKCβII levels with overall survival outcomes.
Main Methods:
- Immunohistochemical analysis of PKCβII, BCL-2, and cell of origin in pretreatment samples from 95 DLBCL patients receiving rituximab with CHOP/CHOEP.
- Kaplan-Meier survival analyses and multivariate analysis were performed.
- Validation using gene expression data from an independent cohort of 233 DLBCL patients treated with rituximab and CHOP-like chemotherapy.
Main Results:
- Patients with low PKCβII protein levels showed significantly better 3-year overall survival (94% vs. 76%, P=0.036).
- Low PKCβII expression was a favorable prognostic factor across different International Prognostic Index risk groups and molecular subtypes.
- Independent analysis of mRNA levels confirmed that low PKCβII expression correlated with improved 3-year overall survival (84% vs. 68%, P=0.005) and remained an independent predictor in multivariate analysis.
Conclusions:
- Protein kinase C-beta II expression is a significant independent prognostic marker for overall survival in DLBCL patients undergoing immunochemotherapy.
- These findings support the potential role of PKCβII as a predictive biomarker for treatment response in DLBCL.
