The neuropeptide Adrenomedullin Promoted the Progression of Head and Neck Squamous Carcinoma by Negatively Regulating Tumour Immunity

Abstract

Objective: To investigate the putative regulatory mechanisms and functions of the neuropeptide gene adrenomedullin (ADM) in head and neck squamous cell carcinoma (HNSC). Methods: Publicly available data from the TCGA-HNSC database were utilized to explore the involvement of ADM single gene in HNSC by analyzing RNA expression levels of ADM. The involvement of ADM in tumor immunity was particularly investigated from the aspect of tumor-infiltrating immune cells, immune modulator genes, immune checkpoint genes, Estimate-Immune-Stromal score, and immune clusters’ prognostic values. Statistical analysis of the data pertaining to cancer and non-cancerous samples was performed using R software packages. Many web servers were used in the present analyses, including cBioportal, TIMER, STRING, GeneMANIA, and GEPIA. Results: ADM was found to be significantly upregulated in HNSC tumor samples and associated with worse prognostic outcomes. ADM-significantly correlated genes in HNSC were enriched in several tumor promoting pathways, including cytokine-cytokine receptor interaction, HIF-1 signaling, MAPK signaling, chemokine signaling, AGE-RAGE signaling, Relaxin signaling, viral protein interaction with cytokine and cytokine receptor, and NF-kappa B signaling. ADM is involved in tumor immunity of HNSC by being negatively correlated with several tumor-infiltrating immune cells, including tumor macrophages, T cells, B cells, Treg cells, T helper cells, Th17 cells, NK cells, mast cells, and dendritic cells. The negative correlation was observed between ADM expression and the majority of immunomodulator genes. ADM was also found to be negatively correlated with the Estimate-Stromal-Immune score in HNSC, indicating its involvement in the tumor immune microenvironment. Conclusions: ADM gene may play a significant role in promoting the progression of HNSC by negatively regulating immune cells, mediating cytokine and chemokine signaling, HIF-1 signaling, MAPK signaling, and NF-kappa B signaling. Therefore ADM can be regarded as a valuable candidate biomarker and holds promising prospects in treating head and neck cancer.