Objective To explore the expression levels of the chromosome 5 open reading frame 34 (C5orf34) gene in hepatocellular carcinoma (HCC), and its correlation with clinicopathological features and prognosis.

Methods The expression of C5orf34 in HCC tissues was analyzed using the TIMER, TCGA and THE HUMAN PROTEIN ATLAS databases. The relationship between the survival period of HCC patients and expression of C5orf34 was analyzed online using the Kaplan-Meier Plotter database. The enriched biological functions and pathways of C5orf34 in the high-risk group were predicted by Gene set enrichment analysis (GSEA). The relationship between C5orf34 and immune-infiltrating cells was analyzed using TIMER data.

Results The mRNA and protein expression levels of C5orf34 in HCC tissues were significantly higher than those in normal liver tissues, and the expression level of C5orf34 was significantly correlated with the age, pathological grade and tumor grade. The results of survival analysis indicated that the overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS) in HCC patients with high expression of C5orf34 were significantly shortened. The results of GSEA analysis indicated that the main enriched pathways in the C5orf34 high-expression group included cell cycle, DNA replication, mismatch repair and homologous recombination, etc. The TIMER database analysis showed that the C5orf34 was positively correlated with the expression levels of tumor purity, B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, neutrophils and dendritic cells in the HCC immune microenvironment.

Conclusions The C5orf34 is highly expressed in HCC, and closely related to the occurrence, development and poor prognosis of HCC, and can be used as a biomarker for evaluating the prognosis of HCC.