Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. The purpose of this study was to establish and validate a gene-expression-based prognostic signature in non-metastatic patients with HNSCC.
Materials and methods: All the patients were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We randomly divided the GSE65858 samples into 70% (training cohort, n = 190) and 30% (internal validation cohort, n = 72). A total of 36 samples collected from the TCGA HNSCC databases were selected as an independent external validation cohort. The oligo package in R was used to normalize the raw data before analysis. Data characteristics were extracted, and a gene signature was built via the least absolute shrinkage and selection operator regression model. The predictive model was developed by multivariable Cox regression analysis. T stage, N stage, human papilloma virus status, and the gene signature were incorporated in this predictive model, which was shown as a nomogram. Calibration and discrimination were performed to assess the performance of the nomogram. The clinical utility of this nomogram was assessed by the decision curve analysis.
Results: Overall, 2001 significant messenger RNAs in HNSCC samples were identified compared with normal samples. The gene signature contained seven genes and significantly correlated with overall survival. The gene signature was also significant in subgroup analysis of the primary cohort. The calibration was plotted in the external cohort (C-index 0.90, 95% CI 0.85, 0.95) compared with the training (C-index 0.76, 95% CI 0.73, 0.79) and internal (C-index 0.71, 95% CI 0.66, 0.77) cohorts. In clinic, a decision curve analysis demonstrated that the model including the prognostic gene signature score status was better than that without it.
Conclusion: This study developed and validated a predictive model, which can promote the individualized prediction of overall survival in non-metastatic patients with HNSCC.
Keywords: Cox regression; Lasso regression; gene expression; prognostic; signature.