A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma

Primary breast diffuse large B-cell lymphoma (PB-DLBCL), the most common histologic subtype of lymphoid malignancy in the breast, is a clinically and genetically heterogeneous disease that has insufficient systematic studies on the pathological and molecular features, optimal treatment scheme, as well as the prognostic factors. The aim of our study was to identify biomarkers and distinct subtypes of PB-DLBCLs and then evaluate the prognosis of this rare malignant lymphoma. We carried out hierarchical clustering analysis to evaluate protein expressions of potential biomarkers detected by immunohistochemistry staining of samples from 68 PB-DLBCL patients. The gene expression data from TCGA database was obtained to validate the identified clusters. We identified three robust clusters based on the B-cell receptor (BCR) signaling pathway, including two recognized NF-κB-dependent and PI3K-dependent clusters, and a distinct subset of PB-DLBCL with NF-κB-independent anti-apoptotic overexpression plus PI3K signaling, which exhibited an evolving definition and distinctive characters of a cluster group. Furthermore, survival analysis results showed an inferior outcome in NF-κB-dependent cluster patients and favorable survival in the PI3K-dependent cluster patients, suggesting an important predictive value of the three clusters. Our study provided a new perspective for understanding clinical complexity of PB-DLBCLs, and gave evidence for finding targeted biomarkers and strategies.