Clinically Relevant Proteomic Signature in Hepatocellular Carcinoma Patients with Macrovascular Invasion

ABSTRACT: Vascular invasion is considered as the critical risk factors for tumor recurrence of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) and metastasis in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins in 53 HCC patients with differential vascular invasion. In patients with MaVI, 47 proteins were significantly down-regulated in HCC tumor tissue. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top 3 enriched pathways are urea cycle, gluconeogenesis and arginine biosynthetic process. We validated 9 remarkably dysregulated candidates in HCC patients with MaVI by Western blot, including 8 down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6 and CES1) and 1 up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism were verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Hepatocellular Carcinoma

SUBMITTER: Lei Fang  

LAB HEAD: Lei Fang

PROVIDER: PXD011846 | Pride | 2022-03-02

REPOSITORIES: Pride