A DNA damage repair signature predicted immunotherapy response and clinical prognosis in HNSCC

Abstract Background: DNA damage repair genes were confirmed to play important role in the tumorigenesis and tumor microenvironment. However, the role of DNA damage repair genes in Head and Neck Squamous Cell Carcinoma (HNSCC) is scarce Method: Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC cohort was used to identify the DNA damage repair genes with survival prognosis. Least absolute shrinkage and selection operator (LASSO) regression was used to construct the prognosis model for HNSCC. Survival analysis and receiver operating curve for the HNSCC were used to validate the model. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify the potential pathways associated with the signature model. Gene set enrichment analysis and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the tumor immune environment and immunotherapy response of HNSCC patients. Finally, nomogram was constructed to validate the clinical usefulness of the signature model. Result: We constructed a six-gene DNA damage repair related signature (including DCLRE1C, TOP3B, POLE2, POLD2, ERCC2 and RAD23B). The results of the survival analysis and ROC curve suggested that the signature showed good prognosis value. The risk score based on the signature model was significantly correlated with the immune cell infiltration and expression levels of the immune markers of HNSCC and could predict the immunotherapy response for HNSCC. Finally, a nomogram was constructed and showed good consistent fitness between the predicted and observed values for 1-, 3- and 5-year OS. Conclusion: We developed a DNA damage repair signature for HNSCC, which related to survival prognosis and tumor microenvironment, indicating its usage for clinical management.