ABSTRACT
BACKGROUND: This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. METHODS: 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves. RESULTS: The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability. CONCLUSION: This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.
ABSTRACT
Bone remodeling is a persistent process for maintaining skeletal system homeostasis, and it depends on the dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. Aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, plays a pivotal role in regulating skeletal system. In order to better understand the role of Ahr in bone remodeling, we focused on bone remodeling characteristic, and the effects of Ahr on bone formation and differentiation, which suggest that Ahr is a critical control factor in the process of bone remodeling. Moreover, we discussed the impacts of Ahr on several signaling pathways related to bone remodeling, hoping to provide a theoretical basis to improve bone remodeling.