The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility.

Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Using TCGA data, we analyzed the expression levels of different in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on expression were estimated in analyzed patients. The results for selected were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. We demonstrated that 73% of the analyzed were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of , , , and correlated with patient survival. The four were also upregulated in HPV-positive patients. The elevated expression of those correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of and was associated with immune cell mobilization and better survival rates, while the elevated expression was linked with metastasis formation and worse survival. In this work, we performed a panel of in silico analyses to discover the role of in head and neck squamous cell carcinoma. We found that , , , and correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.