Background: Limited therapeutic options are available for advanced LUAD without driver gene mutations. Anti-CDK therapy has shown effectiveness in several kind of cancers, however, the mechanisms still need to be elucidated.
Materials and methods: The lncRNA associated with CDK1 and the immunomodulatory factors that regulate CDK1 were found by bioinformatics analysis and experimental verification. The prognostic model and immune resistance mechanism of lung adenocarcinoma were revealed by single cell analysis, immune infiltration analysis, and signal pathway analysis.
Results: LINC00261 was found to be an important CDK1-related lncRNA with a better prognosis in LUAD. In addition, high CDK1 expression indicates a poor immunotherapy response, which may be associated with overexpression of CXCL8. CXCL8 decreased in patients who were immunotherapy-responsive but increased in patients who were immunotherapy-resistant. Signaling pathway analysis suggested that increased CXCL8 and decreased LINC00261 may participate in hypoxia-induced tumor angiogenesis and cause a poor prognosis for the patients. CXCL8 and CDK1 may change G2-M transformation and EMT and promote tumor proliferation.
Conclusion: This study explained that LINC00261, CDK1, and CXCL8 may have a mutual regulation relationship, which affects the occurrence of LUAD and the efficacy of immunotherapy.
Keywords: CDK1; CXCL8; LINC00261; lung adenocarcinoma.