title: Retrospective analysis of protein kinase C-beta (PKC-beta) expression in lymphoid malignancies and its association with survival in diffuse large B-cell lymphomas.
abstract: 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 anti-apoptosis, cell proliferation, and B-cell proliferation signaling pathways are functionally related to PKC-beta.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Integrative Biology Informatics, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. lish@lilly.com
authors.forename: Shuyu
authors.initials: S
authors.lastname: Li
authors.forename: Mark
authors.initials: M
authors.lastname: Phong
authors.forename: Michael
authors.initials: M
authors.lastname: Lahn
authors.forename: Leslie
authors.initials: L
authors.lastname: Brail
authors.forename: Susan
authors.initials: S
authors.lastname: Sutton
authors.forename: Boris K
authors.initials: BK
authors.lastname: Lin
authors.forename: Donald
authors.initials: D
authors.lastname: Thornton
authors.forename: Birong
authors.initials: B
authors.lastname: Liao