ArticleBreast cancer research : BCR2020
Age-associated genes in human mammary gland drive human breast cancer progression.
Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 25 citations in OpenAlex.
- BRCAGenie: A machine learning-driven 43-gene polygenic risk score model for precision prediction of breast cancer survival.Journal of translational medicine · 2025Article
- Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era.International journal of molecular sciences · 2024Review
- Patterns of distant metastasis and survival outcomes inFrontiers in endocrinology · 2024Article
- The metastasis patterns and their prognostic features in patients with de novo metastatic breast cancer of different ages.Cancer medicine · 2023Article
- Transcriptome and metabolome analyses reveal the interweaving of immune response and metabolic regulation in pelvic organ prolapse.International urogynecology journal · 2023Article
- The role of DYNLT3 in breast cancer proliferation, migration, and invasion via epithelial-to-mesenchymal transition.Cancer medicine · 2023Article
- A Novel Aging-Related Prognostic lncRNA Signature Correlated with Immune Cell Infiltration and Response to Immunotherapy in Breast Cancer.Molecules (Basel, Switzerland) · 2023Article
- Transcriptomic profiles of age-related genes in female trachea and bronchus.Frontiers in genetics · 2023Article
- Assessing the knowledge, attitudes and barriers regarding health promotion of breast cancer among community pharmacists.Future science OA · 2022Article
- Article
- Reduced Bone Mass in Collagen Prolyl 4-HydroxylaseJBMR plus · 2022Article
- High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer.Frontiers in genetics · 2022Article
- Clinical and pathological features and risk factors for primary breast cancer patients.World journal of clinical cases · 2021Article
- The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma.Biomarker research · 2021Article
- Pharmacists' knowledge, attitudes, beliefs, and barriers toward breast cancer health promotion: a cross-sectional study in the Palestinian territories.BMC health services research · 2021Article
- Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer.Frontiers in oncology · 2021Article
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11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAging is a comorbidity of breast cancer suggesting that aging-associated transcriptome changes may promote breast cancer progression. However, the mechanism underlying the age effect on breast cancer remains poorly understood.
methodWe analyzed transcriptomics of the matched normal breast tissues from the 82 breast cancer patients in The Cancer Genome Atlas (TCGA) dataset with linear regression for genes with age-associated expression that are not associated with menopause. We also analyzed differentially expressed genes between the paired tumor and non-tumor breast tissues in TCGA for the identification of age and breast cancer (ABC)-associated genes. A few of these genes were selected for further investigation of their malignancy-regulating activities with in vitro and in vivo assays.
resultsWe identified 148 upregulated and 189 downregulated genes during aging. Overlapping of tumor-associated genes between normal and tumor tissues with age-dependent genes resulted in 14 upregulated and 24 downregulated genes that were both age and breast cancer associated. These genes are predictive in relapse-free survival, indicative of their potential tumor promoting or suppressive functions, respectively. Knockdown of two upregulated genes (DYNLT3 and P4HA3) or overexpression of the downregulated ALX4 significantly reduced breast cancer cell proliferation, migration, and clonogenicity. Moreover, knockdown of P4HA3 reduced growth and metastasis whereas overexpression of ALX4 inhibited the growth of xenografted breast cancer cells in mice.
conclusionOur study suggests that transcriptome alterations during aging may contribute to breast tumorigenesis. DYNLT3, P4HA3, and ALX4 play significant roles in breast cancer progression.
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