J Cancer 2020; 11(9):2431-2441. doi:10.7150/jca.39083

Research Paper

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

Wenjia Su1*, Xingjian Niu2*, Hongfei Ji3,4, Yang Xu2, Lei Zhong5, Shuye Wang1, Dabei Tang2, Xiaoping Zhou2, Qingyuan Zhang2,3,4✉, Jin Zhou1✉

1. Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin 150081, Heilongjiang, China
2. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, Heilongjiang, China
3. Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin 150081, Heilongjiang, China
4. Heilongjiang Academy of Medical Sciences, Harbin 150081, Heilongjiang, China
5. Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin 150081, Heilongjiang, China
* Wenjia Su and Xingjian Niu contributed equally to this work

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Citation:
Su W, Niu X, Ji H, Xu Y, Zhong L, Wang S, Tang D, Zhou X, Zhang Q, Zhou J. A novel classification based on B-cell receptor signal gene expression correlates with prognosis in primary breast diffuse large B-cell lymphoma. J Cancer 2020; 11(9):2431-2441. doi:10.7150/jca.39083. Available from http://www.jcancer.org/v11p2431.htm

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Abstract

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.

Keywords: Primary breast diffuse large B-cell lymphoma, B-cell receptor signaling pathway, Cluster analysis, Prognosis