Global blood gene expression profiles following a breast cancer diagnosis—Clinical follow-up in the NOWAC post-genome cohort
Open Access
- 8 March 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (3), e0246650
- https://doi.org/10.1371/journal.pone.0246650
Abstract
Objective: This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease. Material and methods: A random distribution of follow-up time from breast cancer diagnosis till blood sampling was obtained by a nested, matched case-control design in the Norwegian Women and Cancer Post-genome Cohort. From 2002–5, women were invited to donate blood samples, regardless of any cancer diagnosis. At end of the study period in 2015, any cancer diagnoses in the 50 000 participants were obtained via linkage to the Norwegian Cancer Registry. For each breast cancer patient (n = 415), an age- and storage time-matched control was drawn. The design gave a uniform, random length of follow-up time, independent of cancer stage. Differences in blood gene expression between breast cancer cases and controls were identified using the Bioconductor R-package limma, using a moving window in time, to handle the varying time elapsed from diagnosis to blood sample. Results: The number of differentially expressed genes between cases and controls were close to 2,000 in the first year after diagnosis, but fell sharply the second year. During the next years, a transient second increase was observed, but only in women with metastatic disease who later died, both compared to invasive cases that survived (p<0,001) and to metastatic cases that survived (p = 0.024). Among the differentially expressed genes there was an overrepresentation of heme metabolism and T cell-related processes. Conclusion: This explorative analysis identified changing trajectories in the years after diagnosis, depending on clinical stage. Hypothetically, this could represent the escape of the metastatic cancer from the immune system.Funding Information
- FP7 Ideas: European Research Council (AdG-232997 TICE)
- Halfdan Jacobsen og frues legat
This publication has 18 references indexed in Scilit:
- The Molecular Signatures Database Hallmark Gene Set CollectionCell Systems, 2015
- Somatic mutation in cancer and normal cellsScience, 2015
- Immune cell promotion of metastasisNature Reviews Immunology, 2015
- limma powers differential expression analyses for RNA-sequencing and microarray studiesNucleic Acids Research, 2015
- Peripheral blood cells inform on the presence of breast cancer: A population‐based case–control studyInternational Journal of Cancer, 2014
- Systems Epidemiology in CancerCancer Epidemiology, Biomarkers & Prevention, 2008
- Gene expression analyses in breast cancer epidemiology: the Norwegian Women and Cancer postgenome cohort studyBreast Cancer Research, 2008
- Model-based variance-stabilizing transformation for Illumina microarray dataNucleic Acids Research, 2008
- Cohort Profile: The Norwegian Women and Cancer Study--NOWAC--Kvinner og kreftInternational Journal of Epidemiology, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005