Overexpression of NRP1 is Associated with Poor Prognosis via Accelerating Immunosuppression in Head and Neck Squamous Cell Carcinoma

Abstract

Background

Neuropilin-1 (NRP1) is a significant molecular structure that participates in many diseases progress including malignant tumors. However, its role in head and neck squamous cell carcinoma (HNSCC) remains to be uncovered. In this study, we determined the function of NRP1 as a crucial biomarker in proliferation, metastasis and immunosuppression in HNSCC.

Methods

We collected samples of normal tissues (n = 18) and HNSCC tissues (n = 202) for immunohistochemical staining of NRP1 and evaluated its correlation to clinical prognostic characteristics. Furthermore, we enrolled 37 HNSCC patients received immune checkpoint blockade (ICB) treatment with defined therapeutic effects records. The biological process, signal pathways, and immune infiltration relevance to NRP1 were analyzed utilized transcriptome data from The Cancer Genome Atlas (TCGA).

Results

The NRP1 protein expression was significantly upregulated in HNSCC tissue and was associated with T stage, N stage, histological differentiation, recurrence and NRP1 expression. The high expression of NRP1 indicated poor survival rate and was found to be an independent prognosis factor. Enrichment analysis showed that NRP1 was associated with cell adhesion, extracellular matrix organization, homophilic cell adhesion via plasma membrane in biological process and neuroactive ligand–receptor interaction, protein digestion and absorption, calcium signal pathways. Moreover, NRP1 mRNA level was found positively correlated to cancer associated fibroblast cells, Treg cells and macrophage/monocyte cells.

Conclusion

NRP1 might be likely to develop into a potential immunoregulation target as well as a predictive biomarker in HNSCC immune treatment.

Keywords:

• NRP1
• head and neck squamous cell carcinoma
• immunosuppression
• prognosis
• bioinformatics

Ethical Approval

This study was approved by the Ethical Committee of the Affiliated Stomatology hospital of Nanjing Medical University (No. PJ2018-051-001). All patients signed the informed consent to participate in this study. We obey the principles of the 1983 Declaration of Helsinki. In other words, all experiments in this paper obey this principle.

Disclosure

The authors declared that they have no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81772887), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 2018-87) and Jiangsu Provincial Health Commission Scientific research project (Z2022080).