Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is known for its high malignancy and poor prognosis. Despite some progress in treatment approaches in recent years, the prognosis of HCC remains unfavorable. CPNE1 (Copine 1), a calcium-dependent phospholipid-binding protein, has been shown to be involved in the development of various cancers. However, the precise role of CPNE1 in HCC and its underlying molecular mechanisms remain unclear. This study aims to elucidate the role of CPNE1 in HCC and investigate its relationship with the immune microenvironment. METHODS: In this study, we conducted a pan-cancer analysis of CPNE1 expression and prognosis using data from the Cancer Genome Atlas (TCGA). Using a series of bioinformatics analyses, including expression, correlation, and survival analyses, we predicted the upstream miRNAs and lncRNAs of CPNE1 and explored its regulatory network through the competitive endogenous RNA (ceRNA) mechanism. Subsequently, functional enrichment analysis was conducted to explore the related functions and signaling pathways of the target genes. Finally, using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data from the GEO database, we analyzed the spatial distribution of CPNE1 in liver cancer tissues and its expression profiles in immune cells. RESULTS: Differential expression analysis revealed that CPNE1 expression is higher in hepatocellular carcinoma tissues than in adjacent non-cancerous tissues, and HCC patients with higher CPNE1 expression tend to have a worse prognosis. The SNHG6-hsa-miR-101-3p axis was identified as a promising CPNE1 upstream ncRNA pathway in HCC. Functional enrichment analysis revealed that CPNE1 is significantly enriched in several tumor-associated pathways. Single-cell sequencing and spatial transcriptomics analyses revealed that CPNE1 expression is elevated in malignant hepatocytes and immune cells, particularly in NK cells. Further cell communication analysis suggested that CPNE1 may influence the immune microenvironment of liver cancer through the MIF and PPIA-BSG signaling pathways. CONCLUSION: CPNE1 is linked to poor prognosis in hepatocellular carcinoma (HCC) and proposes the SNHG6/hsa-miR-101-3p/CPNE1 regulatory axis. The study investigates the role of CPNE1 in modulating the immune microenvironment of liver cancer and suggests that it may serve as a biomarker for poor prognosis in HCC patients.