Global Gene Expression Profiling and Bioinformatics Analysis Reveal Downregulated Biomarkers as Potential Indicators...

Objective: The study aimed to elucidate the significance of CLEC4G, CAMK2β, SLC22A1, CBFA2T3, and STAB2 in the prognosis of hepatocellular carcinoma (HCC) patients and their associated molecular biological characteristics. Additionally, the research sought to identify new potential biomarkers with therapeutic and diagnostic relevance for clinical applications. Methods and Materials: We utilized a publicly available high throughput phosphoproteomics and proteomics data set of HCC to focus on the analysis of 12 downregulated phosphoproteins in HCC. Our approach integrates bioinformatic analysis with pathway analysis, encompassing gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the construction of a protein-protein interaction (PPI) network. Results: In total, we quantified 11547 phosphorylation sites associated with 4043 phosphoproteins from a cohort of 159 HCC patients. Within this extensive data set, our specific focus was on 19 phosphorylation sites displaying significant downregulation (log₂ FC ≤ -2 with p-values < 0.0001). Remarkably, our investigation revealed distinct pathways exhibiting differential regulation across multiple dimensions, including the genomic, transcriptomic, proteomic, and phosphoproteomic levels. These pathways encompass a wide range of critical cellular processes, including cellular component organization, cell cycle control, signaling pathways, transcriptional and translational control, and metabolism. Furthermore, our bioinformatics analysis unveiled noteworthy insights into the subcellular localizations, biological processes, and molecular functions associated with these proteins and phosphoproteins. Within the context of the PPI network, we identified 12 key genes CLEC4G, STAB2, ADH1A, ADH1B, CAMK2B, ADH4, CHGB, PYGL, ADH1C, AKAP12, CBFA2T3, and SLC22A1 as the top highly interconnected hub genes. Conclusions: The findings related to CLEC4G, ADH1B, SLC22A1, CAMK2β, CBFA2T3, and STAB2 indicate their reduced expression in HCC, which is associated with an unfavorable prognosis. Furthermore, the results of KEGG and GO pathway analyses suggest that these genes may impact liver cancer by engaging various targets and pathways, ultimately promoting the progression of hepatocellular carcinoma. These results underscore the significant potential of CLEC4G, ADH1B, SLC22A1, CAMK2β, CBFA2T3, and STAB2 as key contributors to HCC development and advancement. This insight holds promise for identifying therapeutic targets and charting research avenues to enhance our understanding of the intricate molecular mechanisms underlying hepatocellular carcinoma.