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

Abstract

Simin Li

Objective: To investigate the putative regulatory mechanisms and functions of the neuropeptide gene adrenomedullin (ADM) in head and neck squamous cell carcinoma (HNSCC).

Methods: Publicly available data from the TCGA-HNSCC database were utilized to explore the involvement of ADM single gene in HNSCC by analyzing RNA expression levels of ADM. The involvement of ADM in tumour immunity was particularly investigated from the aspect of tumour infiltrating immune cells, immune modulator genes, immune checkpoint genes, Es- timate-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 HNSCC tumour samples and associated with worse prognostic outcomes. ADM-significantly correlated genes in HNSCC were enriched in several tumour promoting pathways including cytokine-cytokine receptor interaction, HIF-1 signaling, MAPK signaling, chemokine signaling, AGE-RAGE signaling, Re- laxin signaling, viral protein interaction with cytokine and cytokine receptor, and NF-kappa B signaling. ADM is involved in tumour immunity of HNSCC by being negatively correlated with several tumor infiltrating immune cells, including tumour 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 majority of immune modulator genes. ADM was also found to be negatively correlated with Estimate-Stromal-Immune score in HNSC, indicating its involvement in tumour immune microen- vironment.

Conclusions: ADM gene may play a significant role in promoting the progression of HNSCC 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.

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