Prefoldin and prefoldin-like complex subunits as predictive biomarkers for hepatocellular carcinoma immunotherapy

Abstract

Background: Prefoldin complex subunits (PFDNs) and prefoldin-like complex subunits (PFDLNs) collaborate in protein folding, modulate endoplasmic reticulum stress. The association between PFDN/PFDLN and the immune microenvironment of HCC remains unclear. We investigated the biological significance of PFDNs and PFDLNs in HCC using bioinformatics.

Methods: The relationship between PFDNs/PFDLNs and HCC was analysed using TCGA, and Human Protein Atlas. The protein-protein interaction (PPI) network was performed through String and Cytoscape. In addition, mutations in PFDNs and PFDLNs were analysed using cBioPortal. Clinical correlation analysis, survival analysis was conducted by using UALCAN and Kaplan-Meier analysis. The protein-protein interaction (PPI) network was performed through String and Cytoscape. The GO and KEGG enrichment analyses were also carried out. CCK-8 and Flow cytometry analysis were used to detect the proliferation and apoptosis of PFDN1 and UXT knockdown HCC cells. Immune infiltrates analyses was were conducted using the TIMER and TISIDB to determine whether PFDNs/PFDLNs are predictive biomarkers of immune cell infiltration.

Results: We observed that PFDNs and PFDLNs were significantly overexpressed in HCC tissues compared to normal liver tissues. This abnormal expression was associated with worse clinicopathological features and negatively affected patient survival. PFDNs and PFDLNs have varying degrees of mutations in HCC, which may be related to their abnormal expression. In addition, up-regulated PFDN1 and UXT were found to promote HCC proliferation and inhibit apoptosis in vitro. Finally, the expression of certain PFDNs and PFDLNs in the tumour microenvironment was positively correlated with the level of tumour-infiltrating immune cells and significantly enhanced the infiltration of immune cells in the microenvironment.

Conclusions: PFDNs and PFDLNs are valuable predictive biomarkers for immune infiltration in HCC and may assist in tumour immunotherapy research and prognosis prediction in the future.

Keywords: Hepatocellular carcinoma; Immunotherapy; Prefoldin subunits; Prefoldin-like complex subunits; Tumour-infiltrating immune cells.