ArticleBMC cancer2022
Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 3 citations in OpenAlex.
- A prospective cohort study of clinical characteristics and outcomes in Chinese patients with estrogen receptor-negative/progesterone receptor-positive early breast cancer.Breast cancer research and treatment · 2023Article
- A nomogram based on cuproptosis-related genes predicts 7-year relapse-free survival in patients with estrogen receptor-positive early breast cancer.Frontiers in oncology · 2023Article
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Authors and funding
12 authors at 5 institutions in 4 countries.
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Abstract
backgroundExperimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue.
methodsWe conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively.
resultsIn the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA.
conclusionGlucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.
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