Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Venetis, Konstantinos; Piciotti, Roberto; Sajjadi, Elham; Invernizzi, Marco; Morganti, Stefania; Fusco, Nicola

doi:10.3390/cells10061377

Cited by 43 publications

(38 citation statements)

References 108 publications

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“…In vivo experiment, 2 mice in the control group started to have grasping weakness 10 days after tumor formation, which is also in line with the characteristics of nerve infiltration and metastasis in the early stage of ACC ( 27 ). The results showed that the dysfunction rate was significantly reduced after RPS3 knockdown.…”

Section: Discussionsupporting

confidence: 64%

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma

et al. 2022

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BackgroundAdenoid cystic carcinoma (ACC) is a malignant tumor in salivary gland tissue, that is characterized by strong invasiveness and lung metastasis, leading to poor survival rates. RPS3 is been reported to be associated with the biological functions of tumor cells. This study explored the regulatory effect of RPS3 in ACC to provide new therapeutic targets for ACC therapy.MethodsWe reviewed the clinical and pathologic data of 73 ACC patients. The expression of RPS3 was examined in ACC by immunohistochemistry. Transwell, wound healing, half-maximal inhibitory concentration (IC50) and other experiments were used to determine the regulatory effect of RPS3 on ACC functions. Coimmunoprecipitation and mass spectrometry analysis were used to detect the binding proteins of RPS3, mechanisms by which RPS3/STAT1/NF-kB signaling regulates ACC behavior were assessed using western blotting (WB), qPCR, etc. To explore the regulatory effect of RPS3 on ACC in vivo, we constructed nude mouse sciatic nerve infiltration model and a lung metastasis model for studies.ResultsHigh RPS3 expression was associated with metastasis and a poor prognosis in ACC patients. Inhibition of RPS3 expression reduced ACC migration, invasion and cisplatin resistance, and overexpression of RPS3 promoted ACC migration, invasion and cisplatin resistance. Further experiments revealed that RPS3 can activate the STAT1/NF-kB signaling pathway and regulate ACC behavior through binding to STAT1. The incidence of sciatic nerve infiltration and lung metastasis in nude mice after RPS3 knockdown was lower than that of the control group in vivo.ConclusionRPS3 is highly expressed and associated with the prognosis and survival of ACC patients. The RPS3/STAT1/NF-kB pathway may play an important regulatory role in ACC migration, invasion and chemoresistance. As a new therapeutic target of ACC, its clinical application value is worthy of attention and further exploration.

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Section: Discussionsupporting

confidence: 64%

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma

et al. 2022

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“…However, young metastatic BC patients might have better prognosis than elderly patients ( 6 ). BC most often metastasizes to the bone, which not only negatively affects the quality of life of patients, but also affects the longevity of patients ( 7 ). Although the diagnosis and treatment of BC has made great progress, bone metastasis is still a significant challenge for clinicians.…”

Section: Introductionmentioning

confidence: 99%

Establishment and Verification of Prognostic Nomograms for Young Women With Breast Cancer Bone Metastasis

Wang

Shao

et al. 2022

Front. Med.

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PurposeThe prognosis of patients with metastatic breast cancer usually varies greatly among individuals. At present, the application of nomogram is very popular in metastatic tumors. The present study was conducted to identify independent survival predictors and construct nomograms among young women with breast cancer bone metastasis (BCBM).Patients and MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database to identify young women diagnosed with BCBM between 2010 and 2016. We first analyzed the potential risk factors of overall survival (OS) and cancer-specific survival (CSS) by applying univariate Cox regression analysis. Then we conducted multivariate Cox analysis to identify independent survival predictors. Based on significant independent predictors, we developed and validated novel prognostic nomograms by using the R version 4.1.0 software.ResultsWe finally identified 715 eligible young women with BCBM for survival analysis, of which 358 patients were in the training set, and 357 patients in the validation set. Approximately four-fifths of patients are between 31 and 40 years old. The 5-year OS and CSS rates of this research population were 41.9 and 43.3%, respectively. Multivariate analysis revealed seven independent predictors of both OS and CSS, including race, tumor subtype, tumor size, surgical treatment, brain metastasis, liver metastasis, and lung metastasis. Based on these predictors, we developed and validated OS and CSS nomograms. The C-index of the OS nomogram reached 0.728 and 0.73 in the training and validation sets, respectively. The C-index of the CSS nomogram reached 0.743 and 0.695 in the training and validation sets, respectively. Meanwhile, high quality calibration plots were revealed in both OS and CSS nomograms.ConclusionThe current novel nomograms can provide an individualized survival evaluation of young women with BCBM and instruct clinicians to treat them appropriately.

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“…Indeed, the PI3K/Akt/mTOR pathway is the most commonly upregulated pathway in HR-and HER2+ breast cancers, being involved in many aspects of cell growth, proliferation, survival, metabolism, and immune response regulation [40]. A deep disturbance of these processes is caused by abnormal activating events targeting PI3K/Akt, which leads to tumorigenesis, metastasis, tumor progression, and therapy resistance [36,[41][42][43]. In addition, PTEN activity in the nucleus is critical for tumor suppression due to the modulation of the DNA damage response and anti-tumor immune activity, independently of PTEN phosphatase activity [44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Combined analysis of PTEN, HER2, and hormone receptors status: remodeling breast cancer risk profiling

et al. 2021

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Background Phosphatase and tensin homolog (PTEN) loss is associated with tumorigenesis, tumor progression, and therapy resistance in breast cancer. However, the clinical value of PTEN as a biomarker in these patients is controversial. We sought to determine whether the benefit of traditional biomarkers testing is improved by the analysis of PTEN status for the identification of high-risk breast cancer. Methods A cohort of 608 patients with breast cancer was included in this study. Based on the expression on the neoplastic cells compared to the normal internal controls by immunohistochemistry (IHC), cases were classified as PTEN-low (PTEN-L) or PTEN-retained (PTEN-WT). The former constituted the study group, while the latter the control group. Analysis of gene expression was performed on publicly available genomic data and included 4265 patients from the METABRIC and MSK cohorts retrieved from cBioPortal. The Shapiro-Wilk test was used to analyze the normal distributions of continuous variables. Relationships between PTEN status and the clinicopathologic and molecular features of the patient population were assessed using Fisher’s exact test or Chi-squared/Wilcoxon rank-sum test. Survival curves were built according to the Kaplan-Meier method. Results Alteration in PTEN status was significantly different at protein and gene levels, where the reduced protein expression was observed in 280/608 cases (46.1%) from our group, while genetic aberrations in only 315/4265 (7.4%) cases of the METABRIC and MSK cohorts. PTEN-L tumors were significantly enriched for hormone receptors (HR) and HER2 negativity (n = 48, 17.1%) compared to PTEN-WT tumors (n = 22, 6.7%; p = 0.0008). Lack of HR with or without HER2 overexpression/amplification was significantly associated with worse overall survival (OS) in PTEN-L but not in PTEN-WT breast cancers (p < .0001). Moreover, PTEN-L protein expression but not gene alterations was related to the outcome, in terms of both OS and disease-free survival (p = 0.002). Conclusions The combined analysis of PTEN, HER2, and HR status offers relevant information for a more precise risk assessment of patients with breast cancer.

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Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Cited by 43 publications

References 108 publications

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma

Establishment and Verification of Prognostic Nomograms for Young Women With Breast Cancer Bone Metastasis

Combined analysis of PTEN, HER2, and hormone receptors status: remodeling breast cancer risk profiling

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