Proteomic profiling of metabolic proteins as potential biomarkers of radioresponsiveness for colorectal cancer

Abstract

Surgery, radiation therapy (RT), and chemotherapy are commonly used treatment modalities for CRC management. The locally advanced CRC is managed with preoperative RT or in combination of chemoradiotherapy whereas palliative RT is recommended for metastatic CRC patients to enhance overall survival and reduce distressing symptoms. There are many biomarkers established based on tumour staging, grading and molecular characteristics of patients (e.g., mutation, DNA methylation, and gene expression profiling). Interestingly, none of these markers are adequately validated for RT scheme. In order to establish the radioresponsive biomarker in CRC, we established a mouse xenograft tumour model and applied radiation to the tumours. We identified 9 metabolic proteins, namely PGK1, PGAM1, ENO1, PKM, TKT, GLUD1, LDHA, GAPDH, and MDH2, which are differentially expressed in tumours with different radioresponsiveness. Furthermore, we validated their expression in tumours from the unirradiated, poorly responded and highly responded tumour groups. In addition, we analysed their expressions in clinical samples from the public database. Extensive literature studies shown that these metabolic proteins are associated with key biochemical pathways including, glycolysis, ammonia detoxification, carcinogenesis, and drug responses. Further studies are needed to translate our findings into clinical use. Significance: With the increasing incidence of colorectal cancer (CRC) globally, it is crucial to establish strategic treatment protocol by personalizing cancer treatment. Despite the well-established treatment protocols for CRC in the past decades, the mortality remains high. There is a trend of applying personalized treatment to improve patient survival. It has been reported that biomarkers may be used to predict treatment outcomes or to adjust individual treatment protocols. This project aims to identify specific metabolic proteins as biomarkers for CRC radioresponsiveness. Using bioinformatical analysis, we have identified 9 metabolic proteins which could be used as potential biomarkers for radiation therapy in CRC tumours.