Abstract
Head-and-neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of neck lymph node metastasis (LNM), a key prognostic factor. Therefore, identifying the biological processes during LNM of HNSCC has significant clinical implications for risk stratification. This study performed Gene Ontology enrichment analysis of differentially expressed genes between tumors with LNM and those without LNM and identified the involvement of immune response in the lymphatic metastasis of HNSCC. We further identified greater infiltrations of CD8+ T cells in tumors than in adjacent normal tissues through immunochemistry in the patient cohort (n = 62), indicating the involvement of CD8+ T cells in the antitumor immunity. Hierarchical clustering analysis was conducted to initially identify the candidate genes relevant to lymphocyte-mediated antitumor response. The candidate genes were applied to construct a LASSO Cox regression analysis model. Three genes were eventually screened out as progression-related differentially expressed candidates in HNSCC and a risk scoring system was established based on LASSO Cox regression model to predict the outcome in patients with HNSCC. The score was calculated using the formula: 0.0636 × CXCL11 - 0.4619 × CXCR3 + 0.2398 × CCR5. Patients with high scores had significantly worse overall survival than those with low scores (p < 0.001). The risk score showed good performance in characterizing tumor-infiltrating lymphocytes and provided a theoretical basis for stratifying patients receiving immune therapies. Additionally, a nomogram including the risk score, age, and TNM stage was constructed. The prediction model displayed marginally better discrimination ability and higher agreement in predicting the survival of patients with HNSCC compared with the TNM stage.