Retrospective analysis of protein kinase C-beta (PKC-β) expression in lymphoid malignancies and its association with survival in diffuse large B-cell lymphomas

Background: Both mechanistic features and recent correlative findings suggest a potential role for protein kinase C-beta (PKC-beta) in tumor pathogenesis, particularly in B-cell malignancies. To evaluate the role of this gene in lymphoid malignancies, we analyzed global gene expression data to quantify PKC-beta expression across diagnostic groups and, when possible, determined correlations between PKC-beta expression and survival. Results: Our analysis showed that the level of PKC-beta expression was highest in chronic lymphocytic leukemia and follicular lymphoma. Within diffuse large-B cell lymphoma (DLBCL), PKC-beta expression was significantly higher in activated B-cell- like subtype than germinal center B-cell-like subtype (P < 0.0001). Elevated PKC-beta appeared to be associated with worse survival in both of these subtypes. When analyzed within clinically defined risk groups established by the International Prognostic Index (IPI), PKC-beta expression was lowest in patients with low IPI scores (0-1). Within intermediate- and high-risk IPI groups, elevated PKC-beta expression was associated with worse survival, suggesting that PKC-beta may expand the prognostic value of the IPI. Results of global gene expression analyses of DLBCL samples corroborate previous observations that antiapoptosis, cell proliferation, and B- cell proliferation signaling pathways are functionally related to PKC-beta. Conclusion: We present a first detailed pharmacogenomics report comparing PKC-beta mRNA expression across different lymphoid malignancies and evaluating it as an outcome predictor. Our findings suggest that DLBCL patients with elevated PKC-beta have a worse prognosis, indicating that further evaluation of PKC-beta as a chemotherapeutic target for lymphoid malignancies is warranted. Reviewers: This article was reviewed by Dr. Pierre Pontarotti, Dr. Kateryna Makova, and Dr. Matthew Coleman ( nominated by Dr. Sandrine Dudoit).