TIAM2 Contributes to Osimertinib Resistance, Cell Motility, and Tumor-Associated Macrophage M2-like Polarization in Lung Adenocarcinoma

Abstract

Background: Osimertinib-based therapy effectively improves the prognosis of lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor mutations. However, patients will have cancer progression after approximately one year due to the occurrence of drug resistance. Extensive evidence has revealed that lipid metabolism and tumor-associated macrophage (TAM) are associated with drug resistance, which deserves further exploration. Methods: An osimertinib resistance index (ORi) was built to investigate the link between lipid metabolism and osimertinib resistance. The ORi was constructed and validated using TCGA and GEO data, and the relationship between ORi and immune infiltration was discussed. Weighted gene co-expression network analysis based on the M2/M1 macrophage ratio determined the hub gene TIAM2 and the biological function of TIAM2 in LUAD was verified in vitro. Results: ORi based on nine lipid metabolism-related genes was successfully constructed, which could accurately reflect the resistance of LUAD patients to osimertinib, predict the prognosis, and correlate with M2-like TAM. Additionally, TIAM2 was found to increase osimertinib tolerance, enhance cell motility, and promote M2-like TAM polarization in LUAD. Conclusions: The lipid metabolism gene is strongly connected with osimertinib resistance. TIAM2 contributes to osimertinib resistance, enhances cell motility, and induces M2-like TAM polarization in LUAD.

Characteristics of Transcriptome and Metabolome Concerning Intramuscular Fat Content in Beijing Black Pigs

“…DGAT2 participated in the control of the lipid metabolic process. This gene is significantly associated with IMF content in pigs and facilitates the deposition of triacylglycerols. − In addition to the enriched genes, some nonenriched genes related to lipid synthesis ( CIDEC , CYP4B1 , FOSL1 , and THRSP ), − lipid metabolism ( TIAM2 and SERPINE1 ), , and adipogenesis ( ARID5B and KLF5 ), , might also contribute increased fat content in high IMF pigs. In the low IMF pigs, up-regulated expression of BST2 , DDX60 , RSAD2 , ISG15 , MX1 , and MX2 was responsible for the biological process of defense response to the virus.…”

Tumor-associated macrophages affect the treatment of lung cancer

“…However, the high M2/M1 ratio in the TME poses a limitation on the maximum benefit from EGFR-TKIs, as it promotes tumor cell tolerance to targeted drugs. The interaction between targeted drugs and macrophages within the TME is complex and can influence sustained benefits for patients through the coordination of an immunostimulatory microenvironment and targeted therapies [ [174] , [175] , [176] ].…”

BDH1‐mediated LRRC31 regulation dependent on histone lysine β‐hydroxybutyrylation to promote lung adenocarcinoma progression

“…CCK-8 assay, colony formation assay, tumor sphere formation assay, wound healing assay, Transwell migration, and invasion assay These methodologies have been comprehensively detailed in previous studies, and in this study, they were performed in line with established protocols. [53][54][55][56]…”