Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy

• Main Authors: Hermawan, Adam, Putri, Herwandhani
• Format: Article PeerReviewed
• Language: English
• Published: Springer 2022
• Subjects: Pharmaceutical Sciences
• Online Access: https://repository.ugm.ac.id/278720/1/Hermawan_FA.pdf; https://repository.ugm.ac.id/278720/; https://bmcgenomdata.biomedcentral.com/articles/10.1186/s12863-022-01086-2; https://doi.org/10.1186/s12863-022-01086-2
• Institution: Universitas Gadjah Mada

Background: Several studies have demonstrated the antitumor activity of rosiglitazone (RGZ) in cancer cells, includ- ing breast cancer cells. However, the molecular targets of RGZ in the inhibition of angiogenesis in breast cancer cells remain unclear. This study aimed to explore the potential targets of RGZ in inhibiting breast cancer angiogenesis using bioinformatics-based analysis. Results: Venn diagram analysis revealed 29 TR proteins. KEGG pathway enrichment analysis demonstrated that TR regulated the adipocytokine, AMPK, and PPAR signaling pathways. Oncoprint analysis showed genetic alterations in FABP4 (14%), ADIPOQ (2.9%), PPARG (2.8%), PPARGC1A (1.5%), CD36 (1.7%), and CREBBP (11%) in patients with breast cancer in a TCGA study. The mRNA levels of FABP4, ADIPOQ, PPARG, CD36, and PPARGC1A were significantly lower in patients with breast cancer than in those without breast cancer. Analysis of gene expression using bc-GenExMiner showed that the mRNA levels of FABP, ADIPOQ, PPARG, CD36, PPARGC1A, and CREBBP were significantly lower in basal-like and triple-negative breast cancer (TNBC) cells than in non-basal-like and non-TNBC cells. In general, the protein levels of these genes were low, except for that of CREBBP. Patients with breast cancer who had low mRNA levels of FABP4, ADIPOQ, PPARG, and PPARGC1A had lower overall survival rates than those with high mRNA levels, which was supported by the overall survival related to DNA methylation. Correlation analysis of immune cell infiltration with TR showed a correlation between TR and immune cell infiltration, highlighting the potential of RGZ for immunotherapy. Conclusion: This study explored the potential targets of RGZ as antiangiogenic agents in breast cancer therapy and highlighted FABP4, ADIPOQ, PPARG, PPARGC1A, CD36, and CREBBP as potential targets of RGZ. These findings require further validation to explore the potential of RGZ as an antiangiogenic agent.