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Comparison of microRNA expression with whole blood between ER positive breast cancer patients and normal controls

ABSTRACT: Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53179 | GEO | 2013/12/12

SECONDARY ACCESSION(S): PRJNA231181

REPOSITORIES: GEO

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Project description:Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2- primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2+ and HER2- subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2- circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2- circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2+ and HER2- circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2- phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance. Seventy-four single candidate CTCs from two representative ER+/HER2- patients (BRx-42 and BRx-82) and 14 triple negative patients were isolated via micromanipulation and subjected to single-cell RNA-sequencing. Thirteen candidate CTCs expressed PTPRC at a level higher than 10 reads-per-million, so were deemed potential White Blood Cells and therefore dropped from further consideration. Expression profiles of CTCs expressing ERBB2 at a level greater than 10 RPM were compared with those expressing ERBB2 at a level less than 10 RPM.

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Comparison of microRNA expression with whole blood between ER positive breast cancer patients and normal controls

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