A miRNA-based signature predicts development of disease recurrence in HER2 positive breast cancer after adjuvant trastuzumab-based treatment

Du, Fangzhi; Yuan, Peng; Zhao, Zhixun; Yang, Zihao; Wang, Tao; Zhao, Jiao; Luo, Yang; Wang, J. Y.; Fan, Ying; Cai, Rong; Zhang, P.; Li, Q.; Song, Yu; Xu, Binghe

doi:10.1038/srep33825

Cited by 29 publications

(56 citation statements)

References 28 publications

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“…The higher expression level of miR-150-5p has been described in BC subtypes, mostly in TNBC [29,49,50], and also in basal I [51] subtypes. It has been described as a good prognostic biomarker for patients with HER2-positive BC [52,53]. Overexpression of miR-150-5p has been described in TNBC tumors [50], specifically in African American TNBC patients in comparison with non-Hispanic White TNBC patients [29].…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

et al. 2020

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MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC.

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Section: Discussionmentioning

confidence: 99%

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

et al. 2020

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“…Several previous studies (summarized in Supplementary Table S6) involving discovery and validation stages have identified miRNA signatures related to breast cancer prognosis (39)(40)(41)(42)(43)(44)(45)(46)(47). These signatures have involved anywhere from two (40) to 22 miRNAs (44), with little overlap in the miRNAs included in the various signatures.…”

Section: Discussionmentioning

confidence: 99%

A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis

et al. 2019

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Dysregulation of miRNA expression may influence breast cancer progression, and experimental evidence suggests that miRNA silencing might suppress breast cancer metastasis. However, the relationship between miRNA and metastasis must be confirmed before this approach can be applied in the clinic. To this end, we conducted a two-stage study in a cohort of 3,760 patients with breast cancer to first identify and then validate the association between miRNA expression and risk of distant metastasis. The first stage (discovery) entailed miRNA sequencing of 126 casecontrol pairs; qPCR was used to validate the findings in a separate set of 80 case-control pairs. The 13 miRNAs most differentially expressed between cases and controls were combined into an miRNA score that was significantly associated with risk of distant metastasis in a logistic regression model that also included clinical variables (tumor size and number of positive lymph nodes) (OR per unit increase in score ¼ 1.30; 95% confidence interval, 1.03-1.66). The results of this study suggest that in women with invasive breast cancer, a miRNA score that incorporates both clinical variables and miRNA expression levels in breast tumor tissue is moderately predictive of risk of subsequent distant metastasis.Significance: A novel predictive scoring system for patients with breast cancer includes clinical variables and the expression levels of 13 miRNAs and may help to identify those at increased risk of distant metastasis. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): T.E. Rohan, S. Weinmann, O. Loudig Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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“…The miRNA processing pathway has long been viewed as linear and universal to all mammalian miRNAs [37]. Numerous miRNAs have been identified as regulators of breast cancer cell properties [59][60][61]. While some miRNAs act as tumor suppressors, others act as oncogenes, depending on their respective molecular targets.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor beta as epigenetic mediator of miR-10b and miR-145 in mammary cancer

et al. 2017

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Even though the role of estrogen receptor alpha (ERα) in the modulation of breast cancer cells' behavior is thoroughly studied, the biological functions of its isoform, ERβ, are less elucidated. The suppression of ERβ in the aggressive ERα-negative MDA-MB-231 breast cancer cells resulted in the inhibition of epithelial to mesenchymal transition (EMT) and major changes in the basic functional properties and expression levels of certain matrix components of breast cancer cells. This arrest in metastatic potential of breast cancer cells suggests the contribution of ERβ in the induction of a more aggressive phenotype in MDA-MB-231 breast cancer cells. The epigenetic alterations are responsible for the ability of the tumor cells to metastasize. Here, we report for the first time that the suppression of ERβ in MDA-MB-231 breast cancer cells leads to significant changes in the expression profiles of specific microRNAs, including miR-10b, miR-200b and miR-145. Growth of MCF-7 and MDA-MB-231 cells in estrogen-free medium has a diverse impact on miRNA expression and the behavior of these cells, suggesting the specific effect of estradiol on the miRNA expression profile depending on the ER status of breast cancer cells. Enhanced miR-10b expression or silencing of miR-145 clearly revealed that these microRNAs can regulate the functional properties, EMT program and the expression of major matrix components known to be implicated in breast cancer aggressiveness. Our data revealed that miR-10b is strongly implicated in the regulation of functional properties, EMT program and Erk1/2 signaling in shERβ MDA-MB-231 cells, thus affecting the extracellular matrix (ECM) composition, including syndecan-1, proteolytic behavior, especially MMP2, MMP7 and MMP9 expression and subsequently the aggressiveness of these cells. Accordingly, the inhibition of miR-145 expression significantly increased the aggressiveness of shERβ MDA-MB-231 cells and induced EMT. Moreover, miR-145 inhibition resulted in important changes in the gene and protein levels of ECM mediators, such as HER2 and several MMPs, whereas it significantly increased the phosphorylated levels of Erk1/2 kinases in these cells, suggesting the crucial role of miR-145 in this signaling pathway. These novel results suggest that the alterations in cell behavior and in ECM composition caused by the suppression of ERβ in MDA-MB-231 cells are closely related to certain epigenetic miRNA-induced alterations. Targeting the ERβ-regulated miR-10b and miR-145 is a promising tool for diagnosis and pharmaceutical targeting in breast cancer.

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A miRNA-based signature predicts development of disease recurrence in HER2 positive breast cancer after adjuvant trastuzumab-based treatment

Cited by 29 publications

References 28 publications

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis

Estrogen receptor beta as epigenetic mediator of miR-10b and miR-145 in mammary cancer

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