Metabolomics and miRNA profiling reveals feature of gallbladder cancer-derived biliary extracellular vesicles

• Published in: Biochemical and biophysical research communications Vol. 705; p. 149724
• Main Authors: Kong, Mingyu, Hong, Da Hee, Paudel, Sanjita, Yoon, Na Eun, Jung, Byung Hwa, Kim, Myounghoi, Kim, Tae Hun, Jeong, Jaemin, Choi, Dongho, Lee, Hyunbeom
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-04-2024
• Subjects: Bile acid; Exosome; Exosomes - metabolism; Gallbladder cancer; Gallbladder Neoplasms - genetics; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phospholipid; PI3K/AKT pathway; Phospholipid; Exosome; Bile acid; Gallbladder cancer; PI3K/AKT pathway
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149724

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.
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.
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.
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.
•Downregulation of phospholipids in the biliary exosomes of gallbladder cancer.•38 metabolites and 36 miRNAs are significantly altered in the gallbladder cancer.•Activation of PI3K/AKT pathway is found in the gallbladder cancer group.