CACYBP expression predicts prognosis in hepatocellular carcinoma: A meta-analysis and bioinformatics validation

Hepatocellular carcinoma (HCC) is one of the most prevalent and inflammation-associated cancers. The potential prognostic value of calcyclin-binding protein (CACYBP) in HCC remains unclear. We aimed to perform meta-analysis to clarify the association of CACYBP expression with prognosis.

We searched various databases to collect all eligible studies. The meta-analysis was performed using Review manager V5.4.1. Gene expression profiling interactive analysis 2 (limma) and differential expression sequencing 2 on R 4.3.3 were used to look for differentially expressed genes. Gene-set enrichment analysis using 4 Gene Ontology databases (molecular function; biological process; cellular component; pathways) was performed using TCGAbiolinks on R. Survival analysis on The Cancer Genome Atlas-HCC was done using gene expression profiling interactive analysis 2.

Four studies were retrieved for meta-analysis. Overall survival (OS) (hazard ratio = 1.08; 95% confidence interval: 1.05-1.10), indicated that high CACYBP expression is associated with worse OS. The Cancer Genome Atlas validation consistently indicated that high CACYBP expression correlates with OS (hazard ratio: 1.24, P-value: .04), indicating a worse prognosis. RNA sequencing analysis identified 2910 differentially expressed genes between high and low CACYBP expression groups. Gene-set enrichment analysis showed that upregulated genes in high CACYBP expressers relate to mitosis, nuclear division, cell cycle, microtubule cytoskeleton, ion channel activity, eIF2 signaling, and DNA damage responses. Conversely, downregulated genes were related to oxidation-reduction, steroid metabolic process, response to hormone stimulus, ethanol/acetone degradation, and immune/inflammatory responses like liver X receptor/retinoid X receptor regulation and complement system.

Our results suggested that CACYBP expression in HCC is associated with enhanced cell proliferation and cell cycle progression, as well as altered metabolic and immune responses, which contribute to the poorer clinical and survival outcomes of patients.