Abstract
The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression of IGJ and immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except for IGHE and IGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. High IGHG1 mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas high IGHA2 mRNA levels were primarily associated with lower age at diagnosis. High IGHA2 and IGJ mRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, high IGHG1 mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.
Highlights
Breast cancer is a heterogeneous disease, which is illustrated by differential expression of estrogen receptor (ER) and progesterone receptor (PR), occasional prevalence of HER2 amplification, and differences in proliferation rate which together provide the basis for the classification of breast cancer in different subgroups
IGJ was highly correlated to both IGHM and the IGHAs, which is in line with IGJ encoding the joining chain necessary for the production of functional IgA dimers and IgM pentamers
The analysis showed a clear association of IGHA2 and IGJ with improved survival whereas no association was seen for IGHG1, in line with the SCAN-B cohort and the Cohort[270]
Summary
Breast cancer is a heterogeneous disease, which is illustrated by differential expression of estrogen receptor (ER) and progesterone receptor (PR), occasional prevalence of HER2 amplification, and differences in proliferation rate which together provide the basis for the classification of breast cancer in different subgroups. The subgrouping has become more elaborate with the use of global mRNA expression analysis that has led to the identification of at least five subtypes of breast cancer—basal-like, HER2-enriched, luminal A, luminal B, and normal-like tumors[1,2,3]. Differences in the genomic stability, somatic driver mutations, and rearrangement patterns, show that different breast cancers represent fundamentally differential biological subsets[4]. The heterogeneity has important implications for prognosis and for choice of adjuvant systemic therapy. For basal-like tumors that are typically negative for both ER expression and HER2 amplification, only chemotherapy is available today
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