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Protein Kinases in Phagocytosis: Promising Genetic Biomarkers for Cancer

Arumilli, S.; Liu, H.

2024-10-11 genetics
10.1101/2024.10.09.617495 bioRxiv
Show abstract

Cancer is a complex disease characterized by genetic and molecular diversity, often involving dysregulation of critical cellular pathways. Recent advances in pan-cancer research have highlighted the importance of shared oncogenic mechanisms across different cancer types, providing new avenues for therapeutic exploration. Protein kinases, particularly those involved in phagocytosis, play pivotal roles in cellular homeostasis and immune response. This study systematically examines the genetic alterations and expression profiles of protein kinases associated with phagocytosis across various cancer types, using data from The Cancer Genome Atlas (TCGA) and other publicly available resources. We analyzed single nucleotide variations (SNVs), copy number variations (CNVs), methylation patterns, and mRNA expression to identify recurring alterations and their associations with survival outcomes. Our findings reveal that MET and MERTK are the most frequently mutated genes, with missense mutations dominating across cancers. CNV analysis shows significant correlations with survival in cancers like UCEC, KIRP, and KIRC, while methylation analysis indicates cancer-specific regulatory patterns affecting gene expression. Differential expression analysis highlights distinct cancer-type-specific expression profiles, with genes like MET and BTK displaying significant variation. Crosstalk pathway analysis further reveals the involvement of these kinases in key cancer-related pathways, such as epithelial-mesenchymal transition (EMT) and apoptosis. Drug sensitivity analysis identifies potential therapeutic targets, with gene expression correlating significantly with cancer cell line responsiveness to specific compounds. These findings underscore the importance of the phagocytotic kinome in cancer biology and suggest potential therapeutic strategies targeting protein kinases to enhance immune response and improve treatment outcomes.

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