Immunotherapy is effective in a subset of head and neck squamous cell carcinoma (HNSCC). However, the unfavorable response rate and inadequate biomarkers for stratifying patients have primarily limited its clinical application. Considering transcriptional factors (TFs) play essential roles in regulating immune activity during HNSCC progression, we comprehensively analyzed the expression alterations of TFs and their prognostic values.
Gene expression datasets and clinical information of HNSCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository. Then, Brain abundant membrane attached signal protein 1 (BASP1) was screened out of differentially expressed TFs by univariate and multivariate survival analysis. Tumor immune dysfunction and exclusion (TIDE) was applied to analyze the response to immunotherapy of BASP1high/low patients. Meanwhile, GO, KEGG and GSEA analyses were used to enrich the pathways between the BASP1high and BASP1low groups. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, EPIC and quanTiseq algorithms were applied to explore immune infiltrations. Also, immune cycle analysis was conducted by ssGSEA. Additionally, lipid peroxidation, glutathione and reactive oxygen species were performed to detect the ferroptosis alternations.
BASP1 was upregulated and associated with poor survival in HNSCC patients. BASP1high patients exhibited better response rates to anti-PD-1 immunotherapy and higher expressions of immune checkpoint inhibitors. GO, KEGG and GSEA analyses indicated that the expression of BASP1 was related to several immune-related pathways and immunogenic ferroptosis signature. The infiltration of activated CD8+ T cells was authenticated to be decreased in BASP1high patients. Furthermore, BASP1 was identified to be positively correlated with T cell dysfunction and immune escape. Moreover, silencing BASP1 triggered ferroptosis in HNSCC cells, representing as increased LDH, lipid peroxidation and ROS levels, and reduced glutathione synthesis
We demonstrated that BASP1 suppressed immunogenic ferroptosis to induce immunosuppressive tumor microenvironment. BASP1 plays a critical role in immune response, and might be a promising classifier for selecting HNSCC patients who benefit from current immunotherapy.