ArticlePloS one2011
Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Prognostic value of RANK signalling in breast cancer: a systematic review and meta-analysis.BMJ open · 2025Pooled it
- Crucial microRNAs and genes of human primary breast cancer explored by microRNA-mRNA integrated analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Pooled it
- Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer.Scientific reports · 2020Trial
- Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in early-stage breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Cancer medicine · 2018Trial
- Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657).Breast cancer research and treatment · 2017Trial
- Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients.BioMed research international · 2014Trial
- The Presence of SFRP1 Reduces the High Risk of Metastasis in RANKL-Expressing Canine Mammary Cancers.Animals : an open access journal from MDPI · 2026Article
- Neoadjuvant Chemotherapy Plus Denosumab Compared to Chemotherapy Alone in Hormonal Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Premenopausal Breast Cancer Patients.World journal of oncology · 2025Article
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Correlation of RANK and RANKL with mammographic density in primary breast cancer patients.Archives of gynecology and obstetrics · 2024Article
- Unveiling the therapeutic promise: exploring Lysophosphatidic Acid (LPA) signaling in malignant bone tumors for novel cancer treatments.Lipids in health and disease · 2024Review
- RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer.Geburtshilfe und Frauenheilkunde · 2024Article
- RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients.Cancer biomarkers : section A of Disease markers · 2024Article
- Jaw Bone Invasion of Oral Squamous Cell Carcinoma Is Associated with Osteoclast Count and Expression of Its Regulating Proteins in Patients and Organoids.Journal of clinical medicine · 2023Article
- OncoTheradJournal of cancer research and clinical oncology · 2023Article
- Mitigation of Hepatotoxicity via Boosting Antioxidants and Reducing Oxidative Stress and Inflammation in Carbendazim-Treated Rats UsingMolecules (Basel, Switzerland) · 2023Article
- RANKL biology.Bone · 2022Review
- Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration.Scientific reports · 2022Article
- Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.International journal of molecular sciences · 2022Article
- Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReceptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. MATERIALS AND
methodsWe examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival.
resultsMicroarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029).
conclusionsThis is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.
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Registered trials
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