Research on the expression, prognostic value, and regulatory effects on immune microenvironment of NETO2 in oral squamous cell carcinoma

Background: NETO2 is a gene with potential prognostic value in various cancers, but its role in oral squamous cell carcinoma (OSCC) remains unclear. This study investigates NETO2 expression, clinical significance, and its association with the tumor immune microenvironment in OSCC.

Methods: NETO2 expression in OSCC tissues was analyzed using public databases and correlated with prognosis via Kaplan-Meier survival analysis. A nomogram incorporating NETO2 and clinical factors was developed to predict survival, and its performance was assessed using ROC curves. Single-cell RNA Sequencing (scRNA-seq) analyzed cell types and NETO2 expression across different cell populations. The relationships between NETO2 expression, tumor mutation burden (TMB), immune microenvironment, and drug sensitivity were explored, and molecular docking assessed NETO2's binding affinity with small-molecule compounds. The functional role of NETO2 in OSCC cell invasion, proliferation, and migration was validated experimentally.

Results: NETO2 was significantly overexpressed in OSCC tissues, and high expression correlated with shorter overall survival (OS) and progression-free survival (PFS). The nomogram model, developed using TCGA and GEO cohorts, demonstrated good predictive performance, with AUC values for 1-, 3-, and 5-year survival rates above 0.66 in both cohorts. scRNA-seq revealed elevated NETO2 expression in T cell clusters and significant associations with key immune signaling pathways, such as cytokine-cytokine receptor interactions and T cell receptor signaling. The high NETO2 expression group exhibited higher immune cell infiltration, increased potential for immunotherapy response, and differential sensitivity to various Anticancer drugs. Molecular docking showed strong binding of NETO2 with compounds like ruxolitinib, paclitaxel, and docetaxel. Additionally, NETO2's role in OSCC cell invasion, proliferation, and migration was experimentally confirmed.

Conclusion: NETO2 is a significant prognostic biomarker in OSCC, potentially influencing tumor progression through modulation of the immune microenvironment. Its therapeutic targeting warrants further investigation.

Immune microenvironment; NETO2; Oral squamous cell carcinoma; Prognostic biomarker; ScRNA-seq.