Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus-related hepatocellular carcinoma

The present study aimed to investigate the clinical significance and prospective molecular mechanism of cystatin (CST) genes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The role of CST genes in the molecular mechanism of HCC was revealed through bioinformatics analysis. The clinical significance of CST genes was investigated using GSE14520-derived data from patients with HBV-related HCC. Gene set enrichment analysis (GSEA) was used to identify pathways in which the CST genes were enriched, as well as the association between these pathways and HCC. The expression levels of CST1, CST2, CST5, CSTA and CSTB genes were higher in HCC tissue compared with in normal tissue; conversely, CST3 and CST7 were reduced in HCC tissue. Subsequent receiver operating characteristic analysis of the CST genes demonstrated that CST7 and CSTB genes may function as potential diagnostic markers for HCC. Furthermore, the expression levels of CST6 and CST7 were strongly associated with recurrence-free survival and overall survival of patients with HBV-related HCC. GSEA of the CST genes revealed that CST7 was significantly enriched in tumor evasion and tolerogenicity, cancer progenitors, liver cancer late recurrence, liver cancer progression and several liver cancer subclasses. In addition, CST genes demonstrated homology in terms of protein structure and were revealed to be strongly co-expressed. The present findings suggested that CST7 and CSTB genes may serve as potential prognostic and diagnostic biomarkers for HCC.