Signal peptidase complex catalytic subunit SEC11A upregulation is a biomarker of poor prognosis in patients with head and neck squamous cell carcinoma.

In the current study, we aimed to investigate the expression of the five microsomal signal peptidase complex (SPC) subunit genes (SEC11A, SEC11C, SPCS1, SPCS2, and SPCS3) in head and neck squamous cell carcinoma (HNSC) and to explore their prognostic value. Data from the HNSC subset of The Cancer Genome Atlas (TCGA) and one previous single-cell RNA-seq dataset was used. Subgroup analysis was conducted in tumors from different anatomic sites. Gene set enrichment analysis (GSEA), and immune cell infiltration analysis were performed to check the influence of SEC11A on the tumor microenvironment. Among the genes significantly upregulated in the tumor group, only SEC11A expression (as a continuous variable) is independently associated with poorer progression-free survival (PFS) (HR: 2.075, 95%CI: 1.447-2.977, p<0.001) and disease-specific survival (DSS) (HR: 2.023, 95%CI: 1.284-3.187, p = 0.002). Subgroup analysis confirmed the prognostic value in tumors from three anatomic origins, including laryngeal squamous cell carcinoma, oral cavity-related squamous cell carcinoma, and oropharynx-related squamous cell carcinoma. SEC11A is expressed in all subtypes of cells in the tumor microenvironment. Its expression showed a moderate positive correlation with its gene-level copy number (Pearson's r = 0.53, p<0.001). SEC11A expression was negatively correlated with CD8+ T cells and B cells, but was positively correlated with cancer-associated fibroblast and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. In summary, SEC11A upregulation is a result of gene amplification in head and neck squamous cell carcinoma. Its upregulation might serve as an independent prognostic biomarker and a predictor of the infiltration of certain types of immune cells.