Proteomic signatures of radioresistance: Alteration of inflammation, angiogenesis and metabolism-related factors in radioresistant oesophageal adenocarcinomav

ABSTRACT: The clinical management of locally advanced oesophageal adenocarcinoma (OAC) commonly involves neoadjuvant chemoradiotherapy (CRT), but complete pathological response to CRT only occurs in 20-30% of patients, as radioresistance remains a major clinical challenge. In this study we used an established isogenic cell line model of radioresistant OAC to detect proteomic signatures of radioresistance in order to identify novel potential molecular and cellular targets of radioresistance in OAC. Intracellular proteins obtained from radiosensitive (OE33P) and radioresistant (OE33R) cells were subjected to LC-MS/MS analysis. We identified 5785 proteins of which 251 were significantly modulated in OE33R cells, when compared to OE33P. Gene ontology and pathway analysis of the significantly modulated proteins demonstrated altered metabolism in radioresistant cells accompanied by an inhibition of apoptosis in OE33R cells. In addition, radioresistant cells were predicted to have an activation of inflammatory and angiogenic pathways when compared to the radiosensitive cells. For the first time, we performed a comprehensive proteomic profiling of our established isogenic cell line model of radioresistant OAC, providing insights into the molecular and cellular pathways which regulates radioresistance in OAC, and we provided pathway specific signatures of radioresistance that will aid further studies on the development of targeted therapies and personalised approaches to radiotherapy, with the ultimate goal of improving response to radiotherapy in cancer patients.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelium Of Esophagus, Barrett's Esophagus

DISEASE(S): Esophagus Adenocarcinoma

SUBMITTER: David Matallanas  

LAB HEAD: David Matallanas

PROVIDER: PXD020303 | Pride | 2022-08-18

REPOSITORIES: Pride