Alterations of plasma exosomal proteins and metabolites are associated with the progression of castration-resistant prostate cancer

This is the authors' abstract. We don't add key points for this paper.

Current diagnosis tools for prostate cancer, such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis markers for castration-resistant prostate cancer. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profiles of exosomes and to evaluate their potential value for the PCa diagnosis, especially CRPC. Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls, PCa and CRPC patients. The expression of specific exosomal proteins was further validated by targeted 4D-parallel reaction monitoring mass spectrometry. The levels of exosome-derived LRG1 and ITIH3 in the CRPC group were 1.7 and 2.04 times respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed a ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 significantly enhance the malignant phenotype of PCa cells. Furthermore, PCa cell-derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. In conclusion, our results indicated that proteomic and metabolic signatures of exosomes may facilitate discrimination of CRPC from PCa and TFC patients as potential markers. Exosomal LRG1 may involve in PCa malignant progression.