Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer

TY - JOUR

T1 - Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer

AU - Larsson, Christer

AU - Ehinger, Anna

AU - Winslow, Sofia

AU - Leandersson, Karin

AU - Klintman, Marie

AU - Dahl, Ludvig

AU - Vallon-christersson, Johan

AU - Häkkinen, Jari

AU - Hegardt, Cecilia

AU - Manjer, Jonas

AU - Saal, Lao

AU - Rydén, Lisa

AU - Malmberg, Martin

AU - Borg, Åke

AU - Loman, Niklas

PY - 2020/7/6

Y1 - 2020/7/6

N2 - 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.

AB - 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.

U2 - 10.1038/s41523-020-0170-2

DO - 10.1038/s41523-020-0170-2

M3 - Article

C2 - 32656317

VL - 6

JO - npj Breast Cancer

JF - npj Breast Cancer

SN - 2374-4677

IS - 1

M1 - 28

ER -