In silico finding of key pathways and genes that are correlated with induction of cancer during aging of blood

Blood is a critical type of connective tissue that plays a pivotal role in the human body's physiological functions and in maintaining homeostasis. As individuals age increase, the functional efficacy of this tissue diminishes, leading to the onset of numerous pathologies, particularly malignancies (۱,۲). Presently, aging with a reduced incidence of disease and cancer has become a hot topic in humanity; thus, researchers are actively investigating pathways that cause disease and cancer within aged tissues, such as blood. Identifying these pathways and their subsequent targeting may provide a means of mitigating cancer risk associated with increasing age (۳). Consequently, this study aims to elucidate the major pathways and genes implicated in the oncogenesis in aged blood cells by applying bioinformatics methodologies. Method: The gene expression profile designated as GSE۷۵۳۳۷ was extracted from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) among cohorts consisting of six young individuals, eight middle-aged individuals, and six elderly individuals were quantified utilizing the DESeq package within R software. Additionally, the biological pathways associated with the upregulated genes were elucidated via the EnrichR database. The identification of hub genes was conducted using platforms such as the STRING database and Cytoscape software. Result: Our analytical findings revealed that ۲۰۱ genes in the middle-aged group and ۸۰۵ genes in the elderly people exhibited an adjusted P-value of less than ۰.۰۵ and a log-fold change exceeding one. The genes upregulated in the blood of the middle-aged group significantly influenced interferon-alpha/beta signaling; conversely, no notable pathways were detected within the elderly group. Previous investigations have indicated that IFN-α/β, through the activation of the NF-κB signaling pathway, can promote cell survival and confer protection to tumor cells against apoptotic stimuli (۴). In the protein-protein interaction network of the middle-aged blood, CCL۲, NEFL, and CXCL۱۱ demonstrated the highest degrees of connectivity and betweenness centrality, whereas in the blood of the elderly group, GDNF, SHH, and CDH۱۱ emerged as hub genes. Prior studies have established that CCL۲, known as monocytic chemotactic protein ۱ (MCP-۱), neurofilament light polypeptide (NEFL), glial cell-derived neurotrophic factor (GDNF), Sonic Hedgehog (SHH), and Cadherin‐۱۱ are involved in tumorigenesis, particularly head and neck cancers, and gliomas (۵-۹). Conclusion: Our computational analysis revealed that the predominant pathways and genes associated with the aging of blood exhibit a robust correlation with cancer development, suggesting that targeting them may significantly reduce the incidence of cancer among the elderly population.

کلیدواژه ها:

GSE۷۵۳۳۷ ، DEGs ، IFN-α/β ، NF-κB