Abstract
BACKGROUND: We aim to investigate the potential value of cuproptosis-related lncRNA signaling in predicting clinical prognosis and immunotherapy and its relationship with drug sensitivity in head and neck squamous cell carcinoma (HNSCC). METHODS: We first identified the lncRNAs associated with cuproptosis genes in HNSCC and then conducted a series of analytical studies to investigate the expression and prognostic significance of these lncRNAs. Finally, we used RT-qPCR to validate our findings in a laryngeal squamous cell carcinoma cell line and 12 pairs of laryngeal squamous cell carcinoma and adjacent normal tissues. RESULTS: We identified 11 differentially expressed lncRNAs that were associated with cuproptosis genes in HNSCC and also served as prognostic markers for this cancer. Enrichment analysis revealed that these lncRNAs were related to immune-related functions that were suppressed in patients with oncogene mutations in the high-risk group. The patients with a high tumor mutation burden exhibited poor overall survival (OS). We used the tumor immune dysfunction and exclusion model to show that the patients in the high-risk group had great potential for immune evasion and less effective immunotherapy. We also identified several drugs that could be effective in treating HNSCC. Experimental validation showed that AC090587.1 and AC012184.3 exhibited differential expression between the TU686 and HBE cell lines, and SNHG16 showed differential expression among the TU686, TU212, and control HBE cells. Among the 12 pairs of cancer and adjacent tissues collected in the clinic, only SNHG16 showed differential expression. Targeted therapy against SNHG16 holds promise as a prospective novel strategy for the clinical management of HNSCC.