Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer
NPJ BREAST CANCER
Authors: Larsson, Christer; Ehinger, Anna; Winslow, Sofia; Leandersson, Karin; Klintman, Marie; Dahl, Ludvig; Vallon-Christersson, Johan; Hakkinen, Jari; Hegardt, Cecilia; Manjer, Jonas; Saal, Lao; Ryden, Lisa; Malmberg, Martin; Borg, Ake; Loman, Niklas
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 IGHGT 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.
Epigenome-wide methylation differences in a group of lean and obese women - A HUNT Study
SCIENTIFIC REPORTS
Authors: Kvaloy, Kirsti; Page, Christian Magnus; Holmen, Turid Lingaas
Abstract
Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illumina Infinium HumanMethylation450 BeadChip was used in a leucocyte epigenome-wide association study (EWAS) to quantify differential DNA methylation in 60 lean compared with 60 obese young women. Replication was done in monozygotic twins discordant for obesity. At adolescence and adulthood, the two weight groups differed significantly in obesity-related traits and metabolic risk factors. Differential hypomethylation was overrepresented in obese compared to lean women. In the adjusted model, the EWAS revealed 10 differentially methylated CpG sites linked to 8 gene loci COX6A1P2/FGD2, SBNO2, TEX41, RPS6KA2, IGHE/IGHG1/IGHD, DMAP1, SOCS3, and SETBP1- and an enhancer locus at chromosome 2 (2p25.1). The sites linked to TEX41, IGHE/IGHG1/IGHD, DMAP1, and SETBP1 were novel findings, while COX6A1P/FGD2, SBNO2, RPS6KA2, and SOCS3 had been identified previously with concordant direction of effects. RPS6KA2, DMAP1, and SETBP1 were replicated in the BMI-discordant monozygotic twin cohort using the FDR of 5%.