Published online Oct 15, 2022. doi: 10.4251/wjgo.v14.i10.1933
Peer-review started: May 21, 2022
First decision: July 13, 2022
Revised: July 23, 2022
Accepted: September 12, 2022
Article in press: September 12, 2022
Published online: October 15, 2022
As a proteoglycan, VCAN exists in the tumor microenvironment and regulates tumor proliferation, invasion, and metastasis, but its role in hepatocellular carcinoma (HCC) has not yet been elucidated.
To investigate the expression and potential mechanism of action of VCAN in HCC.
Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, we explored the correlation between VCAN expression and clinical features, and analyzed the prognosis of patients with high and low VCAN expression. The potential mechanism of action of VCAN was explored by Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis. We also explored immune cell infiltration, immune checkpoint gene expression, and sensitivity of immune checkpoint [programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA4)] inhibitor therapy in patients with different VCAN expression. VCAN mRNA expression and VCAN meth
VCAN was highly expressed in HCC tissues, which was associated with a poor prognosis in HCC patients. No significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC, but there was a significant difference in VCAN methylation between the two groups. The correlation between VCAN and infiltrations of several different tumor immune cell types (including B cells, CD8+ T cells, and eosinophils) was significantly different. VCAN was strongly related to immune checkpoint gene expression and tumor mutation burden, and could be a biomarker of sensitivity to immune checkpoint (PD1/CTLA4) inhibitors. In addition, VCAN mRNA expression was associated with hepatitis B e antigen, HBV DNA, white blood cells, platelets, cholesterol, and coagulation function.
High VCAN level could be a possible biomarker for poor prognosis of HCC, and its immunomodulatory mechanism in HCC warrants investigation.
Core Tip: VCAN expression is significantly higher in hepatocellular carcinoma (HCC) tumor tissue than in adjacent tissue, and high VCAN level may be a possible biomarker for the diagnosis and prognosis of HCC. VCAN is associated with hepatitis B e antigen in hepatitis B virus infected patients. VCAN may play a role in HCC through the extracellular matrix signaling pathway and inflammatory immune response, and is a potential biomarker for immune checkpoint (programmed cell death protein 1/cytotoxic T lymphocyte antigen 4) inhibitors.