Colorectal Cancer Chemotherapy Drug Bevacizumab May Induce Muscle Atrophy Through CDKN1A and TIMP4

Abstract

The muscle in the organism has the function of regulating metabolism. Long-term muscle inactivity or the occurrence of chronic inflammatory diseases are easy to induce muscle atrophy. Bevacizumab is an antiangiogenic drug that prevents the formation of neovascularization by inhibiting the activation of VEGF signaling pathway. It is used in the first-line treatment of many cancers in clinic. Studies have shown that the use of bevacizumab in the treatment of tumors can cause muscle mass loss and may induce muscle atrophy. Based on bioinformatics analysis, this study sought the relationship and influence mechanism between bevacizumab and muscle atrophy. The differences of gene and sample expression between bevacizumab treated group and control group were studied by RNA sequencing. WGCNA is used to find gene modules related to bevacizumab administration and explore biological functions through metascape. Differential analysis was used to analyze the difference of gene expression between the administration group and the control group in different muscle tissues. The key genes timp4 and CDKN1A were obtained through Venn diagram, and then GSEA was used to explore their biological functions in RNA sequencing data and geo chip data. This study studied the role of bevacizumab in muscle through the above methods, preliminarily determined that timp4 and CDKN1A may be related to muscle atrophy, and further explored their functional mechanism in bevacizumab myotoxicity.

Exploring molecular mechanisms underlying the pathophysiological association between knee osteoarthritis and sarcopenia

“…However, some studies also indicated that the low expression of CDKN1A was associated with the proliferation of fibroblast-like synoviocytes which is one of the manifestations of KOA [ 80 ]. In sarcopenia, CDKN1A contribute to the age-associated decrease in satellite cell proliferation, which causes the muscle atrophy [ 81 ]. CEBPB is an important transcription factor regulating the expression of genes involved in immune and inflammatory responses [ 82 , 83 ].…”