MinGyu Kong Hong, Da Hee Sanjita Paudel Naeun Yoon Jung, Byung Hwa Kim, Myounghoi Kim, Tae Hun Jeong, Jaemin Choi, Dongho Lee, Hyunbeom 2024-04-25T01:09:17Z 2024-04-25T01:09:17Z 2024-04-24 2024-04 0006-291X https://pubs.kist.re.kr/handle/201004/149730 Background Although there are several studies in the development of various human cancers, the role of exosomes is poorly understood in the progression of gallbladder cancer. This study aims to characterize the metabolic changes occurring in exosomes obtained from patients with gallbladder cancer compared with those from other gallbladder disease groups. Methods Biliary exosomes were isolated from healthy donors (n = 3) and from patients with gallbladder cancer (n = 3), gallbladder polyps (n = 4), or cholecystitis (n = 3) using a validated exosome isolation kit. Afterward, we performed miRNA profiling and untargeted metabolomic analysis of the exosomes. The results were validated by integrating the results of the miRNA and metabolomic analyses. Results The gallbladder cancer group exhibited a significant reduction in the levels of multiple unsaturated phosphatidylethanolamines and phosphatidylcholines compared to the normal group, which resulted in the loss of exosome membrane integrity. Additionally, the gallbladder cancer group demonstrated significant overexpression of miR-181c and palmitic acid, and decreased levels of conjugated deoxycholic acid, all of which are strongly associated with the activation of the PI3K/AKT pathway. Conclusions Our findings demonstrate that the contents of exosomes are disease-specific, particularly in gallbladder cancer, and that altered metabolites convey critical information regarding their phenotype. We believe that our metabolomic and miRNA profiling results may provide important insights into the development of gallbladder cancer. English Academic Press Metabolomics and miRNA profiling reveals feature of gallbladder cancer-derived biliary extracellular vesicles Article 10.1016/j.bbrc.2024.149724 1 Biochemical and Biophysical Research Communications, v.705 Biochemical and Biophysical Research Communications 705 N scie scopus 001218639200001 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article MICRORNAS BLOOD BILE-ACIDS METASTASIS Exosome Gallbladder cancer Bile acid Phospholipid PI3K/AKT pathway