Identification and Validation of LOXL2 as a Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma through Multi-Omics and Functional Analysis

Aims: This study aimed to identify novel prognostic biomarkers for lung adenocarcinoma (LUAD) and elucidate their roles in tumor progression through the application of a multi-omics approach.Main methods: Differentially expressed genes related to LUAD were identified using genome-wide and transcriptomics data, along with single-cell RNA sequencing. A Cox proportional hazards model was employed to evaluate the prognostic significance and survival impact of these genes. Functional enrichment and Mendelian randomization analyses were conducted to elucidate the biological pathways and causal roles of lysyl oxidase-like 2 (LOXL2) expression. These analyses were further supported by experiments conducted on cell lines.Key findings: LOXL2 has been identified as a significant prognostic biomarker in LUAD, with high expression levels correlating with poor overall survival. Functional enrichment analyses revealed that LOXL2 is involved in extracellular matrix-receptor interactions and the PI3K-Akt signaling pathways. Immune infiltration analyses revealed a correlation between elevated LOXL2 levels and an immunosuppressive cancer microenvironment, characterized by an increase in regulatory T cells and M2 macrophages, along with a reduction in cytotoxic CD8+ T cells. LOXL2 knockdown led to decreased tumor cell proliferation, enhanced apoptosis, and cell cycle arrest. Furthermore, elevated LOXL2 levels increased sensitivity to chemotherapeutic agents such as cisplatin, suggesting potential benefits for personalized treatment strategies.Significance: These findings suggest that LOXL2 may serve as a valuable prognostic biomarker and therapeutic target in LUAD, with potential implications for patient stratification and personalized therapy.