To investigate the expression profile of family with sequence similarity 83 member A (FAM83A) in lung adenocarcinoma (LUAD) and whether it contributes to tumor progression through cell cycle regulation, as well as to evaluate its potential as a prognostic biomarker and potential therapeutic target.

The expression pattern and clinical relevance of FAM83A were analyzed based on public databases including TCGA, TIMER, and DepMap. Functional enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), while single-sample GSEA (ssGSEA) was applied to assess immune cell infiltration. The association between FAM83A expression and drug sensitivity was evaluated using the GSCALite database. In addition, immunohistochemistry was performed to detect FAM83A expression in LUAD tissues. In NCI-H441 cells, FAM83A was knocked down using siRNA, and its mRNA expression was measured by qRT-PCR. Protein expression levels of FAM83A, CDK1, p-CDK1, Cyclin B1, E2F1, and γ-H2 AX were detected by Western blotting. Cell proliferation, migration, invasion, apoptosis, and cell cycle distribution were evaluated using CCK-8 assays, transwell assay, and flow cytometry, respectively.

FAM83A was highly expressed in LUAD tissues (P<0.0001), and its expression was associated with T stage, N stage, clinical stage, and overall survival in LUAD patients (P<0.05). Functional enrichment analysis showed that FAM83A-related differentially expressed genes (DEGs) were mainly enriched in cell cycle, nuclear division, chromosome segregation, MYC signaling, epithelial-mesenchymal transition, TNFα/NF-κB signaling, hypoxia, and IL-17 signaling pathways. FAM83A expression was correlated with the infiltration levels of multiple immune cell types and responses to selected drugs (P<0.05). Immunohistochemical assay showed that FAM83A expression was higher in LUAD tissues than in adjacent normal tissues (P<0.05). In vitro experiments demonstrated that FAM83A knockdown inhibited the proliferation, migration, and invasion, promoted apoptosis, and induced G2/M phase arrest, accompanied by downregulated CDK1, p-CDK1, Cyclin B1, and E2F1 proteins in LUAD cells.

FAM83A is highly expressed in LUAD and associated with poor prognosis. It may participate in tumor progression through E2F/CDK1-mediated cell cycle regulation, while synergistically affect tumor biological behaviors through multiple tumor-related pathways. FAM83A may serve as a potential prognostic biomarker and therapeutic target for LUAD.