β2-Adrenergic receptor expression is associated with biomarkers of tumor immunity and predicts poor prognosis in estrogen receptor-negative breast cancer

Kurozumi, Sasagu; Kaira, Kyoichi; Matsumoto, Hiroshi; Hirakata, Tomoko; Yokobori, Takehiko; Inoue, Kentaro; Horiguchi, Jun; Katayama, Ayaka; Koshi, Hiromi; Shimizu, Akira; Oyama, Tetsunari; Sloan, Erica K.; Kurosumi, Masafumi; Fujii, Takaaki; Shirabe, Ken

doi:10.1007/s10549-019-05341-6

Cited by 25 publications

(17 citation statements)

References 41 publications

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“…A previous study has revealed that in cells with low ER expression, ferroptosis was easier to be triggered by sulfasalazine in breast cancer cells ( Ou et al, 2016 ). Besides, the correlation between ER and tumor immunity has been also extensively researched ( Kurozumi et al, 2019 ; Romero et al, 2020 ; Smida et al, 2020 ). Therefore, the candidate drugs targeting estrogen receptor are likely to involve in the downstream tumor immunity through ferroptosis.…”

Section: Resultsmentioning

confidence: 99%

Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma

Chen

Yan

et al. 2021

Front. Cell Dev. Biol.

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BackgroundGlioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes.MethodsWe revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map.ResultsThe 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs.Conclusionwe identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.

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Section: Resultsmentioning

confidence: 99%

Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma

Chen

Yan

et al. 2021

Front. Cell Dev. Biol.

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“…Obviously, different cancers may have varying properties to cause local recurrence or metastases, i.e., tumour biology differs, and the activation of adrenergic-inflammatory stimulus may differ, e.g., triple-negative breast cancer is associated with a stronger adrenergic response than other breast cancers [ 69 ], and it is close at hand to suspect variations in adrenergic response between different other cancers. Therefore, if anaesthetic drugs modify tumour biology, the resulting effect may vary between different cancers.…”

Section: Discussionmentioning

confidence: 99%

Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Enlund

2021

Cancers

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Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

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“…The expression of αARs and βARs also differs between cancer cells lines and across molecular subtype (ER, PR, and HER2 status, reviewed in [58]). β2AR is the most widely expressed βAR in basal and luminal breast cancer cell lines and in tumor samples from patients with breast cancer [58,[121][122][123]. β2AR expression was found to correlate with poor prognosis of ER − breast cancer patients [123].…”

Section: Sympathetic Innervation Of the Skeleton And Evidence For An Interplay With The Process Of Bone Metastasismentioning

confidence: 97%

“…β2AR is the most widely expressed βAR in basal and luminal breast cancer cell lines and in tumor samples from patients with breast cancer [58,[121][122][123]. β2AR expression was found to correlate with poor prognosis of ER − breast cancer patients [123]. In another study, β2AR expression was associated with lower disease-free survival and higher lymph node metastasis rates in a small cohort of HER2 + breast cancer patients [121], but opposing results were obtained in another small cohort of HER2 + patients where it was associated with improved disease-free survival [124].…”

Section: Sympathetic Innervation Of the Skeleton And Evidence For An Interplay With The Process Of Bone Metastasismentioning

confidence: 99%

Mechanisms Supporting the Use of Beta-Blockers for the Management of Breast Cancer Bone Metastasis

Madel

Elefteriou

2021

Cancers

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The skeleton is heavily innervated by sympathetic nerves and represents a common site for breast cancer metastases, the latter being the main cause of morbidity and mortality in breast cancer patients. Progression and recurrence of breast cancer, as well as decreased overall survival in breast cancer patients, are associated with chronic stress, a condition known to stimulate sympathetic nerve outflow. Preclinical studies have demonstrated that sympathetic stimulation of β-adrenergic receptors in osteoblasts increases bone vascular density, adhesion of metastatic cancer cells to blood vessels, and their colonization of the bone microenvironment, whereas β-blockade prevented these events in mice with high endogenous sympathetic activity. These findings in preclinical models, along with clinical data from breast cancer patients receiving β-blockers, support the pathophysiological role of excess sympathetic nervous system activity in the formation of bone metastases, and the potential of commonly used, safe, and low-cost β-blockers as adjuvant therapy to improve the prognosis of bone metastases.

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β2-Adrenergic receptor expression is associated with biomarkers of tumor immunity and predicts poor prognosis in estrogen receptor-negative breast cancer

Cited by 25 publications

References 41 publications

Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma

Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma

Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Mechanisms Supporting the Use of Beta-Blockers for the Management of Breast Cancer Bone Metastasis

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