Prognostic Matrisomal Gene Panel and Its Association with Immune Cell Infiltration in Head and Neck Carcinomas

Simple Summary: Squamous cell carcinoma of the head and neck (SCCHN) is a heterogeneous group of tumors arising from squamous cells lining different anatomic sites. This type of malignancy has been mainly investigated by focusing primarily on tumor cells, but recent evidence highlighted the importance of the tumor microenvironment (TME) in cancer growth, progression and metastasis. Hence, we hypothesized that dysregulated matrisomal components could have a common association with patient survival, irrespective of the subsite of origin of the SCCHN. Using bioinformatic methods and public datasets, we successfully identified a gene panel with prognostic value in HPV-negative and non-metastatic node-negative tumors and demonstrated its association with immune cell infiltration. Squamous cell carcinoma of the head and neck (SCCHN) is common worldwide and related to several risk factors including smoking, alcohol consumption, poor dentition and human papillomavirus (HPV) infection. Different etiological factors may influence the tumor microenvironment and play a role in dictating response to therapeutics. Here, we sought to investigate whether an early-stage SCCHN-specific prognostic matrisome-derived gene signature could be identified for HPV-negative SCCHN patients (n = 168), by applying a bioinformatics pipeline to the publicly available SCCHN-TCGA dataset. We identified six matrisome-derived genes with high association with prognostic outcomes in SCCHN. A six-gene risk score, the SCCHN TMI (SCCHN-tumor matrisome index: composed of MASP1, EGFL6, SFRP5, SPP1, MMP8 and P4HA1) was constructed and used to stratify patients into risk groups. Using machine learning-based deconvolution methods, we found that the risk groups were characterized by a differing abundance of infiltrating immune cells. This work highlights the key role of immune infiltration cells in the overall survival of patients affected by HPV-negative SCCHN. The identified SCCHN TMI represents a genomic tool that could potentially aid patient stratification and selection for therapy in these patients.