A DNA damage repair associated signature for HNSCC

Abstract Background: DNA damage repair (DDR) genes play a vital role in tumorigenesis and the tumor microenvironment. However, the specific role of DDR genes in head and neck squamous cell carcinoma (HNSCC) is not fully understood. Method: Gene expression profiles from the TCGA HNSCC cohort were used to identify DNA damage repair genes with prognostic value. LASSO regression was used to construct a prognostic model for HNSCC. Survival analysis and receiver operating characteristic (ROC) curve analysis were used to validate the model. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify potential pathways associated with the signature model. Gene set enrichment analysis (GSEA) and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the tumor microenvironment and immunotherapy response of HNSCC patients, respectively. Finally, a nomogram was constructed to validate the clinical usefulness of the signature model. Result: We constructed a six-gene DNA damage repair-related signature consisting of DCLRE1C, TOP3B, POLE2, POLD2, ERCC2, and RAD23B. The results of survival analysis and receiver operating characteristic (ROC) curve analysis suggested that the signature had good prognostic value. The risk score based on the signature model was significantly correlated with immune cell infiltration and expression levels of immune markers in HNSCC, and could predict the immunotherapy response for HNSCC patients. Finally, a nomogram was constructed and showed good consistent fitness between the predicted and observed values for 1-, 3-, and 5-year overall survival (OS). Conclusion: We developed a DNA damage repair signature for HNSCC that is associated with survival prognosis and the tumor microenvironment, suggesting its potential for clinical management.