Abstract
BACKGROUND: Zinc finger and SCAN domain containing 9 (ZSCAN9), also known as zinc finger factor 193 (ZNF193), has been associated with the enhanced expression of X-chromosomal genes in certain organs. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study examines the mechanism of ZSCAN9 in HCC and analyze its expression, prognostic value, clinical relevance, immune correlation, signaling pathways, and drug sensitivity, thus providing new insights into its potential as a therapeutic target for HCC. METHODS: The Tumor Immune Estimation Resource (TIMER) 2.0 database was used to analyze the pancancer expression of ZSCAN9, its differential expression between tumor and normal tissues, and the associations with overall survival (OS) and recurrence-free survival (RFS). Additionally, The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were used to analyze the pathways, immune levels, and drug sensitivity related to ZSCAN9's involvement in HCC. RESULTS: ZSCAN9 was differentially expressed in HCC, with its high expression being associated with poor prognosis (P<0.05). ZSCAN9 was also correlated with several biological functions, such as DNA replication, G2M checkpoint, tumor proliferation, DNA repair (R>0.3; P<0.05), and fatty acid degradation (R<-0.3; P<0.05). The results of immune correlation analysis showed that ZSCAN9 was positively correlated with the abundance of T helper cells (R>0.2; P<0.05) and negatively correlated with that of dendritic cells (DCs), cytotoxic cells, neutrophils, plasmacytoid DCs, B cells, and interdigitating DCs (R<-0.2; P<0.05). ZSCAN9 was positively correlated with CD274 level (R=0.29), and the results of drug sensitivity analysis indicated that patients with high ZSCAN9 were more responsive to several drugs, including sorafenib, 5-fluorouracil, etoposide, and AKT inhibitor VIII, as compared to those with low expression. CONCLUSIONS: ZSCAN9 may be a biological target capable of predicting recurrence and survival time in patients with HCC and may be involved in the regulation of angiogenesis; moreover, its expression may influence the drug sensitivity of sorafenib, 5-fluorouracil, etoposide, and AKT inhibitor VIII.