Proteomics

Dataset Information

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A novel approach for the discovery of biomarkers of radiotherapy response in breast cancer


ABSTRACT: Radiotherapy is a commonly used treatment modality for the local control of breast cancer. However, the clinical signs of radiotherapy response are often not apparent for several weeks post-treatment. We currently lack tools to predict and/or monitor tumor responses during treatment. The aim of this study was to identify tumor secreted biomarkers of radiotherapy response. Estrogen receptor positive (ER+) MCF-7 cells were serum-starved for 2 h, and were then exposed to various doses of radiation (0, 2, 4, 6, 8 or 10 Gy). Conditioned media (CM) was harvested at 1, 2, 4, 8 and 24 h post-radiation for each radiation dose. Samples underwent processing for liquid chromatography-mass spectrometry (LC-MS) following collection. 33 proteins at the 24 h time point were found to have significantly increased secretion levels (up to 12-fold) at all radiation doses compared to untreated cells. To validate the secretomic results and to further investigate the potential use of these proteins as biomarkers of radiosensitivity, the secreted protein levels of candidate biomarkers were assessed through western blot (WB). WB analysis was performed using CM samples to assess the secretion levels from parental and radioresistant (RR) cell lines (developed within our lab) 24 h after the cells had received a single radiation dose of 2 Gy. Secretion levels of our candidate biomarkers were found to be significantly increased from the radiosensitive MCF-7 cells treated with 2 Gy of radiation at 24 h compared to 24 h untreated controls. In comparison, candidate biomarker levels in the CM samples from untreated and radiation-treated MCF-7 RR cells remained low. Currently there are no validated predictive biomarkers to monitor radiotherapy responses during treatment. These biomarkers could have a clinical role in personalising radiotherapy dosing schedules and durations for solid tumours in the neoadjuvant and palliative setting.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Jimi Wills  

LAB HEAD: Arran Turnbull

PROVIDER: PXD027572 | Pride | 2021-08-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MCF7_1h_0Gy.raw Raw
MCF7_1h_10Gy.raw Raw
MCF7_1h_2Gy.raw Raw
MCF7_1h_4Gy.raw Raw
MCF7_1h_6Gy.raw Raw
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Publications

Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine.

Meehan James J   Gray Mark M   MartĆ­nez-PĆ©rez Carlos C   Kay Charlene C   McLaren Duncan D   Turnbull Arran K AK  

Journal of personalized medicine 20210715 7


Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to  ...[more]

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