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.

• Authors: Lu Liang, Hua He, Shiyao Jiang, Yueying Liu, Jingjing Huang, Xiaoyan Sun, Yi Li, Yiqun Jiang, Li Cong
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 18 (Sep 08 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36142328 (Publication Type: Journal Article)

Chemical References

• Acrylamides
• Aniline Compounds
• Guanine Nucleotide Exchange Factors
• Indoles
• Pyrimidines
• TIAM2 protein, human
• osimertinib
• ErbB Receptors

Topics

• Acrylamides
• Adenocarcinoma of Lung (drug therapy, genetics)
• Aniline Compounds
• Cell Line, Tumor
• Cell Movement (genetics)
• ErbB Receptors (genetics)
• Guanine Nucleotide Exchange Factors
• Humans
• Indoles
• Lung Neoplasms (drug therapy, genetics, pathology)
• Pyrimidines
• Tumor-Associated Macrophages