Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer.

Abstract

PURPOSE:

Lymphocytic infiltration of tumors predicts improved survival in patients with breast cancer. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.

EXPERIMENTAL DESIGN:

Using The Cancer Genome Atlas mRNA-seq data and a large microarray dataset, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.

RESULTS:

Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with SHM.

CONCLUSION:

Taken together, these data suggest the presence of a productive and potentially restricted antitumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors.

• Authors: Michael D Iglesia, Benjamin G Vincent, Joel S Parker, Katherine A Hoadley, Lisa A Carey, Charles M Perou, Jonathan S Serody
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 14 Pg. 3818-29 (Jul 15 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24916698 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• RNA, Messenger
• Receptors, Antigen, B-Cell

Topics

• B-Lymphocytes (metabolism)
• Breast Neoplasms (genetics, immunology, metabolism, mortality)
• Disease-Free Survival
• Female
• Humans
• Mutation
• Neoplasms, Basal Cell (genetics, immunology, metabolism, secondary)
• Ovarian Neoplasms (genetics, immunology, metabolism, mortality)
• Prognosis
• Proportional Hazards Models
• RNA, Messenger (genetics)
• Receptors, Antigen, B-Cell (genetics, metabolism)
• Sequence Analysis, RNA
• Transcriptome