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Radiation-induced GEPs in immortalized and primary breast cells

ABSTRACT: Today, Radiation therapy (RT) regimens are often used for many types of cancer including breast cancer (BC) disease. BC is an heterogeneous disease, at both clinical and molecular levels, presenting distinct subtypes associated with different clinical outcomes. This variability response may be caused by some factors linked to radiation or dependent to BC specific features such as tumor stage and hormone receptor (HR) status. We analyze and compare molecular responses, in term of gene expression profile (GEP) changes, induced by 9 and 23Gy of ionizing radiation (IR) in immortalized and primary cell cultures grouped according their Estrogen (ER) and Progesteron (PR) receptors positive or negative expression. Our explorative study gives some comprehensive hallmarks of the effects of the irradiation in BC cells. We trust that this study could have a role in driving RT towards personalised treatments, based also on the molecular characterization in BC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108962 | GEO | 2018/06/06

REPOSITORIES: GEO

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Project description:Breast carcinoma (BC) is the leading cause of death in women worldwide, making up 23% of all cancers in women, with 1.38 million new cases worldwide annually and responsible for 460,000 deaths. Despite the significant advances in the identification of molecular markers and different modalities of treatment in primary BC, the ability to predict the metastatic behavior in breast cancer is still limited. The purpose of this study was to help identify novel molecular markers associated with clinical outcome in a cohort of Brazilian BC patients. We generated global gene expression profiles from 24 patients with invasive ductal BC followed for â¥ 5-years, including 15 samples from patients classified as presenting good prognosis based on traditional markers and clinical criteria and 9 patients that developed metastasis. We identified a set of 58 differentially expressed genes (p â¤0.01) between groups of patients with good and poor prognosis. Up-regulation of B3GNT7, PPM1D, TNKS2, PHB and GTSE1 in patients with poor prognosis was confirmed by quantitative RT-PCR in an independent sample set from patients with BC (47 with good prognosis and 8 that presented metastasis). Expression of BAD protein was investigated by immunohistochemistry in 1276 BC samples and confirmed the reduced expression levels in metastatic cases observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinoma samples according to clinical course and progression of the disease. Global expression profiles from 38 ductal breast tumor patient samples were used to search for molecular signatures correlated with current prognostic markers. A subset of 24 cases comprising 15 patients that remained free of disease after surgery and 9 patients that developed metastasis was used to identify candidate biomarkers associated with metastatic progression. Candidates were subsequently validated in additional independent samples by RT-qPCR or immunohistochemistry.

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Radiation-induced GEPs in immortalized and primary breast cells

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