LINC00638/hsa-miR-29b-3p axis-mediated high expression of CDCA4 correlates with tumor immune infiltration and hepatocellular carcinoma progression.

Abstract

This study sought to explore the role of cell division cycle-associated protein 4 (CDCA4) in liver hepatocellular carcinoma (LIHC) patients. The RNA-sequencing raw count data and the respective clinical information of 33 different LIHC cancer and normal tissues were collected from the Genotype Tissue Expression (GTEX) and The Cancer Genome Atlas (TCGA) databases. The expression of CDCA4 in LIHC was determined via the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. The PrognoScan database was used to examine the correlation between CDCA4 and overall survival (OS) in LIHC. The interaction between the potential upstream microRNAs and the long non-coding RNAs (lncRNAs) and CDCA4 was explored using the Encyclopedia of RNA Interactomes (ENCORI) database. Finally, the biological role of CDCA4 in LIHC was investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)analyses. CDCA4 RNA expression was elevated in the LIHC tumor tissues and linked to adverse clinical characteristics. It was also upregulated in most tumor tissues in the GTEX and TCGA data sets. According to the receiver operating characteristic (ROC) curve analysis, CDCA4 is a potential a biomarker for the diagnosis of LIHC. According to the Kaplan-Meier (KM) curve analysis, patients with LIHC in TCGA data set with low expression levels of CDCA4 had better than high expression levels in OS, disease-specific survival (DSS), and progression free interval (PFI). The gene set enrichment analysis (GSEA) suggested that CDCA4 mainly affected the biological events of LIHC by participating in the cell cycle, T cell receptor signaling pathway, DNA replication, glucose metabolism, and mitogen activated protein kinase (MAPK) signaling pathway. Based on the competing endogenous RNA concept and the correlation, expression, and survival analysis results, we believe that LINC00638/hsa miR-29b-3p/CDCA4 should be a potential regulatory pathway in LIHC. The low expression of CDCA4 significantly improves the prognosis of LIHC patients, and CDCA4 is a potential new biomarker for LIHC prognosis prediction. CDCA4-mediated LIHC carcinogenesis may involve tumor immune evasion and anti-tumor immunity. LINC00638/hsa-miR-29b-3p/CDCA4 should be a potential regulatory pathway in LIHC, and these findings provide a new perspective for the development of anti-cancer strategies in LIHC.