Co-expression of NRP1 and p-EGFR in the prognosis of patients with head and neck squamous cell carcinoma

Background Aberrant activation of the epidermal growth factor receptor (EGFR) signaling pathway is critically involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). While the monoclonal antibody cetuximab has demonstrated significant efficacy in the initial treatment of HNSCC, the development of drug resistance has limited its therapeutic success. Consequently, identifying novel therapeutic targets and overcoming resistance mechanisms remain urgent priorities. Methods Immunohistochemical staining was used to analyze the expression of neuropilin-1 (NRP1) and phosphorylated epidermal growth factor receptor (p-EGFR) in 202 cases of HNSCC tissue specimens, and the relationship between expression levels and clinicopathological characteristics and patient prognosis was studied. Additionally, the correlation between NRP1 and p-EGFR expression levels was further investigated. Finally, the potential relationship between high expression of NRP1 and EGFR was studied by gene enrichment analysis in TCGA database. Results High expression of NRP1 and p-EGFR was observed in 97 and 90 of the 202 HNSCC tissues, respectively. 78 cases showing co-high expression of both markers. High expression of NRP1 and p-EGFR was significantly associated with lymph node staging, tumor recurrence, and poor prognosis. Patients with co-high expression of NRP1 and p-EGFR exhibited the worst clinical outcomes. Pearson correlation and linear regression analyses revealed a positive correlation between NRP1 and p-EGFR expression levels. Transcriptomic data from TCGA further supported these findings, showing that tissues with high NRP1 expression were significantly enriched for gene set of EGFR pathway activation and resistance to EGFR inhibitors. Conclusions This study demonstrates that high expression of NRP1 and p-EGFR is closely associated with lymph node staging, recurrence, and poor prognosis in HNSCC patients. The positive correlation between NRP1 and p-EGFR expression provides a theoretical foundation for future research targeting NRP1 to mitigate cetuximab resistance and improve therapeutic outcomes.