Global Gene Expression Profiling and Bioinformatics Analysis Reveal Downregulated Biomarkers as Potential Indicators for Hepatocellular Carcinoma

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.