Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression

Reyes, Monica E.; Fujii, Takeo; Branstetter, Daniel; Krishnamurthy, Savitri; Masuda, Hiroko; Wang, Xiaoping; Reuben, James M.; Woodward, Wendy A.; Edwards, Beatrice J.; Hortobágyi, Gabriel N.; Tripathy, Debu; Dougall, William C.; Eckhardt, Bedrich L.; Ueno, Naoto T.

doi:10.1007/s10549-017-4233-5

Cited by 35 publications

(20 citation statements)

References 31 publications

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“…In another study, the RANKL rs9533156 polymorphism was found to be significantly different between patients and healthy individuals and T allele was observed to be more common among patients with breast cancer (26). Reyes et al demonstrated that RANK/ RANKL co-expression was related to survival in triple negative breast cancer (27). Our findings show that t allele may play a protective role in contrast to other studies.…”

Section: Discussioncontrasting

confidence: 72%

Tri̇ple-Negati̇f Meme Kanseri̇ Hastalarinda Rank, Rankl Ve Opg Genleri̇ndeki̇ Poli̇morfi̇zmleri̇n Beli̇rlenmesi̇ Ve Kemi̇k Metastazi Üzeri̇ne Etki̇si̇ni̇n İncelenmesi̇

Yıldız

Saadoni

Aliustaoğlu

et al. 2019

Clinical and Experimental Health Sciences

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A B STR A CT Objective: Triple negative breast cancer (TNBC) is a sub-type of breast cancer with the worst prognosis and highest risk of mortality. Bone metastasis is the most common metastasis type among women with breast cancer. RANK and OPG, are the members of the family of tumor necrosis factor (TNF), which is effective on osteoblastic and osteoclastic mechanisms. RANKL, interacts with RANK and leads to bone resorption, whereas it inhibits bone destruction when it interacts with OPG. Methods: In this study, we investigated the polymorphisms of RANK, RANKL and OPG genes and their effects on bone metastasis in 45 patients with triple negative breast cancer and 30 healthy controls, using PCR, RFLP and agarose gel electrophoresis techniques. Results: The RANKL genotype and allele distribution analysis revealed a significantly increased CC genotype incidence in patients with TNBC and bone metastasis (p=0.011) and in those without bone metastasis (p=0.004) compared to the control group. The OPG genotype and allele distribution analysis revealed significantly increased C allele incidence in patients with TNBC and bone metastasis (p=0.004) compared to the control group. Likewise, the CC genotype (p=0.001) and C allele incidences (p=0.001) were observed to be significantly increased in patients with TNBC compared to healthy controls. Conclusion: This study is one of the first studies investigating all three RANK/RANKL/OPG gene polymorphisms and the relationship between breast cancer and bone metastasis in our country. We believe that our study will shed light onto further studies to be conducted on triple negative breast cancer and bone metastasis.

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Section: Discussioncontrasting

confidence: 72%

Tri̇ple-Negati̇f Meme Kanseri̇ Hastalarinda Rank, Rankl Ve Opg Genleri̇ndeki̇ Poli̇morfi̇zmleri̇n Beli̇rlenmesi̇ Ve Kemi̇k Metastazi Üzeri̇ne Etki̇si̇ni̇n İncelenmesi̇

Yıldız

Saadoni

Aliustaoğlu

et al. 2019

Clinical and Experimental Health Sciences

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“…In another study, patients with low RANKL expression were more likely to develop local recurrence or die from the disease (40). In a different paper, dual expression of RANK and RANKL conferred a negative prognosis and RANKL appeared as an independent prognostic factor (41).…”

Section: Discussionmentioning

confidence: 98%

Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer

Rachner

Kasimir‐Bauer

Göbel

et al. 2019

Clinical Cancer Research

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Purpose: We assessed serum concentrations of the receptor activator of NFkB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), two proteins implicated in the development and progression of breast cancer, in 509 patients with primary, nonmetastatic breast cancer. Then the results were evaluated with regards to the occurrence of bone metastases, the presence of disseminated tumor cells (DTC) in the bone marrow, survival, and risk of developing metastatic disease.Experimental Design: Before surgery, two bone marrow aspirates were analyzed for DTC using density centrifugation followed by immunocytochemistry (pan-cytokeratin antibody A45-B/B3). RANKL and OPG levels in the serum were measured by ELISA.Results: RANKL levels were significantly lower in women >60 years (P < 0.0001) and RANKL/OPG ratios higher in lymph node-positive patients (P < 0.05). High OPG serum levels were associated with a higher risk of death from breast cancer [HR 1.94; 95% confidence interval (CI) 1.23-3.07; P ¼ 0.005] and OPG was an independent prognostic marker for breast cancer-specific survival (BCSS; multivariate analyses, P ¼ 0.035). RANKL levels were 33% higher (P < 0.0001) in DTC pos patients (41%), whereas high levels were associated with a significantly better BCSS in DTC neg patients as compared with low levels (HR 0.524; 95% CI 0.30-0.95; P ¼ 0.04). RANKL serum levels were significantly increased in patients who developed bone metastases (P ¼ 0.01) and patients within the highest quartile of RANKL had a significantly increased risk of developing bone metastases compared with those in the lowest (HR 4.62; 95% CI 1.49-14.34; P ¼ 0.03).Conclusions: These findings warrant further investigation as they provide a rationale for novel diagnostic or therapeutic approaches.NOTE: Values of RANKL and OPG are given in pmol/L. RANKL/OPG is displayed as a ratio of the two values. Significant values (P < 0.05) are shown in bold.Rachner et al.

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“…Then cells were detected using FACS Calibur (BD Biosciences, San Jose, CA);apoptotic cells were quantified by APC + cell ratio. (2) In the cell proliferation assay, after transfection of miRNA, cells were dispersed in 96-wells plate. Each well had 1500 cells, and totally we set 0, 24, 48, 72, 96 h time point.…”

Section: Q-rt-pcrmentioning

confidence: 99%

“…Based on the molecule subtype technology, breast cancer is divided into 5 subtypes, viz., Luminal A, Luminal B, HER2+, Normal like, and Triple Negative 1 . Among them, triple negative breast cancer(TNBC) is characterized by its poor prognosis 2 , high aggressiveness 3 after chemotherapies, and insensitivity towards target therapy 4 . Identifying TNBC-specific aberrant expression of genes or micro (mi) RNAs would not only help inthediagnosis of TNBC patients but can also revealnovel druggable targets in TNBC therapy 5 .…”

mentioning

confidence: 99%

Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer

Wang

et al. 2019

Sci Rep

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Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-β1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-β1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFβ1-EMT axis.

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Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression

Abstract: RANK and RANKL co-expression is associated with poor RFS and OS in patients with TNBC.

Cited by 35 publications

References 31 publications

Tri̇ple-Negati̇f Meme Kanseri̇ Hastalarinda Rank, Rankl Ve Opg Genleri̇ndeki̇ Poli̇morfi̇zmleri̇n Beli̇rlenmesi̇ Ve Kemi̇k Metastazi Üzeri̇ne Etki̇si̇ni̇n İncelenmesi̇

Tri̇ple-Negati̇f Meme Kanseri̇ Hastalarinda Rank, Rankl Ve Opg Genleri̇ndeki̇ Poli̇morfi̇zmleri̇n Beli̇rlenmesi̇ Ve Kemi̇k Metastazi Üzeri̇ne Etki̇si̇ni̇n İncelenmesi̇

Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer

Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer

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