Page 169 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Key signaling proteins in cardiovascular disease

approach is recommended for prospective research. 2.4. Statistical analysis
Furthermore, continuous research into the application of Statistical analyses were performed to evaluate the
this methodology indicates that the core zones of specific enrichment of signaling pathways and the significance of
human PPI networks are highly enriched with vital protein associations within the PPI network. The analysis
proteins and recognized therapeutic targets. The core zones was performed using the clusterProfiler package in R,
display greater enrichment, supporting the hypothesis which integrates GO and Kyoto Encyclopedia of Genes
that this methodology can be beneficial for drug target and Genomes (KEGG) pathway databases. A significance
discovery. 19-23 Building on insights from prior research, threshold of P < 0.01 was applied to determine statistically
the present investigation focuses specifically on zone 1, significant enrichment.
which exhibits extensive cross-linking and is enriched with
proteins associated with diverse cellular functions. 3. Results

2.1. A comprehensive examination of pathways and The investigation focused specifically on the 374 proteins
the enrichment of their functions located in zone 1. To evaluate their contributions to various
pathways associated with CVDs, including heart attacks
To assess the biological importance of different zones and hypertension, these proteins were cross-referenced
within the PPI network, proteins were classified according with those listed in the KEGG pathways. A summary of
to their distance from the core of the network. An analysis the identified pathways is provided in Table 1.
was then conducted to identify specific functions related
to each zone by examining over-representated pathways 3.1. Proteins regulating growth and MAPK cascade
among the protein associated with them. This analysis signaling in zone 1 of the CVD pathway
employed various tools, such as comparative analysis The activation and regulation of signaling cascade pathways
of gene sets from toxicogenomics databases and gene are crucial for the onset and advancement of CVD.
ontology (GO) term enrichment. A statistical threshold of Dysregulation of these pathways can potentially lead to
0.01 was applied to establish the significance of the results. various cardiovascular conditions, such as atherosclerosis,
Furthermore, protein percentages linked to enriched MI, and heart failure. 27,28 Table 2 indicates that signaling
pathways were calculated to assess the potential functional proteins are significantly prevalent across a range of CVD
specialization within the zones.
pathway, constituting 23% of the total protein analyzed.
2.2. A comprehensive investigation of the Following closely are essential proteins, which make up
molecular pathways linked to oncogenes and tumor 17%. Other functional categories are distributed as follows:
suppressor proteins positive signaling (12%), mitogen-activated protein kinase
(MAPK) cascade (12%), growth (8%), negative signaling
To assess the protein expression levels of oncogenes and (8%), and cell cycle (6.3%).
tumor suppressor genes, a thorough assessment was
conducted. This assessment utilized information from 3.2. Proteins associated with programmed cell
extensive genomic sequencing investigations to identify death, oncogenes, and tumor suppressor genes in
pathways displaying enrichment. The main focus of the zone 1 of the CVD pathway
analysis was to examine top-rated interactions, which Oncogenes and tumor suppressor genes have significant
consistently unveiled a recurring pattern. This pattern of impacts on the pathway of CVDs. Numerous studies have
genes was frequently implicated in the development of shown the impact of oncogenes and tumor suppressor
cancer. 24 genes on CVD pathways. 29,30 The hypertension pathway, in
2.3. Crucial proteins involved in cellular functions, particular, involves several oncogenes and tumor suppressor
signaling pathways, growth mechanisms, cell cycle genes. Among these, androgen receptor (AR), guanine
regulation, and their potential as therapeutic nucleotide-binding protein, alpha stimulating (GNAS), and
targets tumor protein p53 (TP53) were identified as critical genes that
To assess zone 1 of PPI network in humans, a method was Table 1. Zone 1 contains a distribution of proteins that are
25
employed in which the consequences of gene knockout closely associated with the pathway of CVD
in mice were examined to identify a group of essential
26
human proteins. This approach enables the identification Pathway type Protein count
of proteins critical for cellular functions, signaling, Heart attacks 26
growth, and regulation of the cell cycle, with potential as Hypertension 84
therapeutic targets. Abbreviation: CVD: Cardiovascular disease.

Volume 9 Issue 1 (2025) 161 doi: 10.36922/ejmo.8086