Abstract
Breast cancer patients with metastatic disease have a higher incidence of deaths from breast cancer than patients with early-stage cancers. Recent findings suggest that there are differences in immune cell function between metastatic and non-metastatic cases, even years before diagnosis. We have analyzed whole blood gene expression by Illumina bead chips in blood samples taken using the PAXgene blood collection system up to two years before diagnosis. The final study sample included 197 breast cancer cases and 197 age-matched controls. We defined a causal directed acyclic graph to guide a Bayesian data analysis to estimate the risk of metastasis associated with the expression of all genes and with relevant sets of genes. We ranked genes and gene sets according to the sign probability for excess risk. Among the screening detected cancers, 82% were without metastasis, compared to 53% of between-screening detected cancers. Among the highest ranking genes and gene sets associated with metastasis risk, we identified plasmacytiod dentritic cell function, the SLC22 family of transporters, and glutamine metabolism as potential links between the immune system and metastasis. We conclude that there may be potentially wide-reaching differences in blood gene expression profiles between metastatic and non-metastatic breast cancer cases up to two years before diagnosis, which warrants future study.
Highlights
IntroductionSurvival of breast cancer has increased substantially [1]
In recent decades, survival of breast cancer has increased substantially [1]
We investigated the relationship between immune system activity, as measured by blood gene expression, and breast cancer metastasis
Summary
Survival of breast cancer has increased substantially [1]. Among breast cancer patients, the proportion of deaths due to breast cancer increases with advanced tumor stage, for metastatic cancer [2]. The fate of a disseminated cancer cell depends on its Metastasis and Blood Gene Expression interactions with the immune cells it encounters during its transit through the circulatory system. A study on node-positive (metastatic) and node-negative (non-metastatic) breast cancer patients showed different mRNA gene expression patterns, both in tumors and lymph nodes, and in the peripheral blood [5]. In the blood cells of non-metastatic patients, gene expression patterns related to lymphocyte activation and B-cells were up-regulated, indicating a systemic down-regulation of immune function in patients with metastasis [5]
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