Identification and cellular validation of the relevant potential biomarkers associated with female lung adenocarcinoma

Abstract

Abstract Background: FOXM1 plays a pivotal role in regulating tumor progression in various cancer types. However, its involvement in the progression of female lung adenocarcinoma (LUAD) and potential impact on immunotherapy remain uncharacterized. Methods: To investigate the role of FOXM1 in LUAD, we conducted a comprehensive analysis using GDC TCGA (Genomic Data Commons The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets along with a Gene Set Enrichment Analysis approach. Our methodology included differential expression analysis, survival correlation analysis, survival correlation meta-analysis, and clinical correlation analysis, all aimed at elucidating the relationship between FOXM1 expression and LUAD. Additionally, the miRDB, miRTarBase, and TargetScan databases were used to predict target microRNAs (miRNAs). Co-expression analysis was performed to explore the interplay between target miRNAs, FOXM1, target long non-coding RNAs, and the estrogen receptor. A competitive endogenous RNA (ceRNA) network was constructed using Cytoscape. The analysis of tumor mutational burden (TMB) was employed to gauge the sensitivity of FOXM1-mutated LUAD to immunotherapy. Furthermore, the Gene Set Enrichment Analysis package facilitated the examination of immune cell infiltration in LUAD samples. Finally, we employed R tools to assess the immunotherapeutic effects of LUAD. We conducted in vitro experiments to evaluate the biological role of FOXM1. Results: FOXM1 expression was elevated in LUAD samples compared to that in normal tissues. Moreover, results from survival and clinical correlation analyses underscored the significant influence of FOXM1 expression on LUAD progression. FOXM1 knockdown has a substantial impact on LUAD cell proliferation and apoptosis. We established a ceRNA network involving DGCR-5, has-miRNA-204-5p, FOXM1, and estrogen receptor 1. Validation experiments confirmed that has-miR-204-5p is a target miRNA for FOXM1, whereas DGCR5 is not a target long non-coding RNAs for has-miR-204-5p. Furthermore, our study demonstrated a physical interaction between FOXM1 and estrogen receptors. Immune-related analyses indicated that the low FOXM1 expression group exhibited increased sensitivity to immunotherapy, including anti-PDA and anti-CTLA treatment. Conclusion: We established a new ceRNA network (DGCR-5---has-miRNA-204-5p---FOXM1---estrogen receptor 1) that holds promise for unraveling mechanistic insights into LUAD and predicting survival outcomes in LUAD patients.