Comprehensive analysis identifies PKMYT1 as an oncogene and potential prognostic and immunological biomarker in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, underscoring the urgent need for novel prognostic biomarkers and therapeutic targets. Although PKMYT1, a serine/threonine protein kinase, is implicated in cell cycle regulation, its comprehensive role and clinical significance in LUAD remain poorly defined. This study aims to investigate the oncogenic function, prognostic value, and immunomodulatory role of PKMYT1 in LUAD. METHODS: We performed integrated multi-omics analyses utilizing data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression, survival, and immune cell infiltration analyses were conducted. Functional enrichment was assessed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Drug sensitivity was predicted in silico. In vitro functional validation included PKMYT1 knockdown in LUAD cell lines followed by assays for proliferation, migration/invasion, and apoptosis. Protein expression was confirmed in clinical LUAD tissues. RESULTS: PKMYT1 was significantly upregulated in LUAD tissues and high expression correlated with poor progression-free survival and overall survival. Multivariate analysis identified PKMYT1 as an independent prognostic factor. PKMYT1 expression was associated with an altered tumor immune microenvironment, specific immune cell infiltration patterns, tumor mutation burden, and immune checkpoint gene expression. High PKMYT1 expression correlated with reduced predicted sensitivity to chemotherapeutic agents. In vitro, PKMYT1 knockdown suppressed LUAD cell proliferation, migration, and invasion while promoting apoptosis, and reversed epithelial-mesenchymal transition. CONCLUSIONS: This study establishes PKMYT1 as a critical oncogene, an independent prognostic biomarker, and a modulator of the tumor immune microenvironment in LUAD. These findings highlight PKMYT1's potential as a promising therapeutic target and a candidate biomarker for patient stratification, offering new insights for targeted therapy strategies in LUAD.