Obesity-related protein biomarkers for predicting breast cancer risk: an overview of systematic reviews

Wu, Xueyao; Zhang, Xiaofan; Yu, Hong‐Ren; Li, Jiayuan

doi:10.1007/s12282-020-01182-0

Cited by 17 publications

(12 citation statements)

References 62 publications

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“…Inferior disease-free and overall survival rates are noted in obese (BMI, ≥30 kg/m 2 ) and overweight (BMI, ≥25–29.9 kg/m 2 ) women with luminal A breast cancer despite being treated with standard endocrine-based therapy 3 . While most studies support an association between obesity and breast cancer and report a 1.25- to 2.5-fold increase in breast cancer recurrence with increased BMI 37 , 38 , obese women with lymph node-negative, ER-positive breast cancer did not show increased recurrence risk and poor response to tamoxifen compared to their lean counterparts 39 . In this clinical trial, inclusion of women with operable tumors and negative axillary lymph nodes only might have led to these results as the study population did not represent a wider spectrum of disease.…”

Section: Discussionmentioning

confidence: 96%

Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB

et al. 2021

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Obese women with hormone receptor-positive breast cancer exhibit poor response to therapy and inferior outcomes. However, the underlying molecular mechanisms by which obesity/hyperleptinemia may reduce the efficacy of hormonal therapy remain elusive. Obese mice with hyperleptinemia exhibit increased tumor progression and respond poorly to tamoxifen compared to non-obese mice. Exogenous leptin abrogates tamoxifen-mediated growth inhibition and potentiates breast tumor growth even in the presence of tamoxifen. Mechanistically, leptin induces nuclear translocation of phosphorylated-ER and increases the expression of ER-responsive genes, while reducing tamoxifen-mediated gene repression by abrogating tamoxifen-induced recruitment of corepressors NCoR, SMRT, and Mi2 and potentiating coactivator binding. Furthermore, in silico analysis revealed that coactivator Med1 potentially associates with 48 (out of 74) obesity-signature genes. Interestingly, leptin upregulates Med1 expression by decreasing miR-205, and increases its functional activation via phosphorylation, which is mediated by activation of Her2 and EGFR. It is important to note that Med1 silencing abrogates the negative effects of leptin on tamoxifen efficacy. In addition, honokiol or adiponectin treatment effectively inhibits leptin-induced Med1 expression and improves tamoxifen efficacy in hyperleptinemic state. These studies uncover the mechanistic insights how obese/hyperleptinemic state may contribute to poor response to tamoxifen implicating leptin-miR205-Med1 and leptin-Her2-EGFR-Med1 axes, and present bioactive compound honokiol and adipocytokine adiponectin as agents that can block leptin’s negative effect on tamoxifen.

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Section: Discussionmentioning

confidence: 96%

Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB

et al. 2021

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“…An overview of systematic reviews explored the association between circulating leptin levels and risk of BC. Higher levels of leptin were found to be associated with an increased risk of premenopausal and postmenopausal BC, suggesting a possible use of this biomarker in a comprehensive risk predictive score for female BC [ 143 , 144 ]. Moreover, leptin receptor (ObR) expression was found to be associated with ER expression and tumor size, suggesting an interaction between the leptin and estrogen systems to promote breast carcinogenesis [ 145 ].…”

Section: Metastasis Propensity and Tumor Microenvironment (Tme)mentioning

confidence: 99%

Propensity for Early Metastatic Spread in Breast Cancer: Role of Tumor Vascularization Features and Tumor Immune Infiltrate

D’Andrea

Cereda

Coppola

et al. 2021

Cancers

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Breast cancer is a complex and highly heterogeneous disease consisting of various subtypes. It is classified into human epidermal growth receptor 2 (HER-2)-enriched, luminal A, luminal B and basal-like/triple negative (TNBC) breast cancer, based on histological and molecular features. At present, clinical decision-making in breast cancer is focused only on the assessment of tumor cells; nevertheless, it has been recognized that the tumor microenvironment (TME) plays a critical biologic role in breast cancer. This is constituted by a large group of immune and non-immune cells, but also by non-cellular components, such as several cytokines. TME is deeply involved in angiogenesis, immune-evasion strategies, and propensity for early metastatic spread, impacting on prognosis and prediction of response to specific treatments. In this review, we focused our attention on the early morphological changes of tumor microenvironment (tumor vasculature features, presence of immune and non-immune cells infiltrating the stroma, levels of cytokines) during breast cancer development. At the same time, we correlate these characteristics with early metastatic propensity (defined as synchronous metastasis or early recurrence) with particular attention to breast cancer subtypes.

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“…Obesity is linked to a higher incidence of postmenopausal estrogen receptor-positive breast cancer and poorer cancer-associated results across the board [7] . The obesity-cancer relationship is thought to be influenced by significant quantities of circulating and local estrogens, changed concentrations of adipokines [8] (adiponectin and leptin), disrupted insulin/IGF signaling, changes in the microbiome, and local and systemic inflammatory effects (e.g., WAT) [7] . The latest studies indicate that obesity-associated insulin/insulin-like growth factor-1 axis, adipokines, inflammatory cytokines and leptin, sex hormones [9] , adiponectin [8] , ORPS [10] , and HER2 [11] proteins play a significant role in breast cancer-related pathways.…”

Section: Introductionmentioning

confidence: 99%

Identification of molecular signatures and pathways of obese breast cancer gene expression data by a machine learning algorithm

Comertpay¹,

Göv²

2022

jtgg

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Aim: Currently, the obesity epidemic is one of the biggest problems for human health. Obesity is impacted on survival in patients with breast cancer. However, key biomarkers of obesity-related breast cancer risk are still not well known. Thus, using machine learning to identify the most appropriate features in obesity-associated breast cancer patients may improve the predictive accuracy and interpretability of regression models. Methods: In the present study, we identified 23 differentially expressed genes (DEGs) from the GSE24185 transcriptome dataset. Seed genes were identified from DEGs, the co-expression network genes and hub genes of the protein-protein interaction network. Pathway enrichment analysis was performed for DEGs. The Ridge penalty regression model was executed by using P-values of enriched pathways and seed gene pathway association score to obtain the most relevant molecular signatures. The model was performed using 10-fold cross-validation to fit the penalized models. Results: Angiotensin II receptor type 1 (AGTR1), cyclin D1 (CCND1), glutamate ionotropic receptor AMPA type subunit 2 (GRIA2), interleukin-6 cytokine family signal transducer (IL6ST), matrix metallopeptidase 9 (MMP9), and protein kinase CAMP-dependent type II regulatory subunit beta (PRKAR2B) were considered as candidate molecular signatures of obese patients with breast cancer. In addition, RAF-independent MAPK1/3 activation, collagen degradation, bladder cancer, drug metabolism-cytochrome P450, and signaling by Hedgehog pathways in cancer were primarily associated with obesity-associated breast cancer. Conclusion: These genes may be used for risk analysis of the disease progression of obese patients with breast cancer. Corresponding genes and pathways should be validated via experimental studies.

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Obesity-related protein biomarkers for predicting breast cancer risk: an overview of systematic reviews

Cited by 17 publications

References 62 publications

Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB

Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB

Propensity for Early Metastatic Spread in Breast Cancer: Role of Tumor Vascularization Features and Tumor Immune Infiltrate

Identification of molecular signatures and pathways of obese breast cancer gene expression data by a machine learning algorithm

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