Serum exosomal DDX17 in the diagnosis and action mechanism of hepatocellular carcinoma

Abstract

This study aimed to explore DDX17 protein expression as a diagnostic biomarker of hepatocellular carcinoma (HCC) and its roles in the occurrence and development of HCC. The proteomics sequencing method was applied to study nine samples of exosomes separated from HCC tissues and corresponding normal non-cancerous tissues. We also performed nanoflow cytometry analysis of DDX17 expression in serum-derived exosomes from 102 HCC patients, 58 persons with liver cirrhosis (LC), and 80 healthy donors (HDs). The feasibility of DDX17 as a diagnostic and prognostic biomarker was evaluated using receiver operating characteristic (ROC) curves. The effects of HCC-derived exosomal DDX17 on LX-2 cell proliferation, migration, and epithelial–mesenchymal transition (EMT) were evaluated through cell proliferation, colony formation, wound healing, transwell migration, and western blotting assays. We found that exosomes produced by HCC cells had much higher levels of DDX17 than those produced by the adjacent non-cancerous tissues. ROC analysis showed that exosomal DDX17 has a strong ability to distinguish HCC with both high sensitivity and high specificity. If the exosomal DDX17 result is negative, then we expect it to be a new kind of diagnostic biomarker. Moreover, we observed that DDX17-positive exosome subtypes isolated from the HepG2 cell line increased cell proliferation, migration, invasion, and EMT in the LX-2 cell line. DDX17-positive exosomes are potential diagnostic biomarkers of HCC and are expected to promote tumor growth, migration, invasion, and EMT.