Gene‑expression signature predicts survival benefit from postoperative chemoradiotherapy in head and neck squamous cell carcinoma

: Postoperative radiotherapy or concurrent chemoradiotherapy are routine clinical options for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the benefit of adding chemotherapy to radiotherapy is contested. The present study aimed to develop a gene signature to predict the clinical benefit of postoperative chemoradiotherapy using public data from The Cancer Genome Atlas. A 22-gene signature was established, which demonstrated the best predictive value. Patients were separated into low-score and high-score subgroups based on the expression score of the 22-gene signature. In the high-score subgroup, patients who received chemoradiotherapy demonstrated improved overall survival, relapse-free survival and local regional control compared with those who received radiotherapy alone. However, in the low-score subgroup adding chemotherapy to radiotherapy was associated with worse patient outcomes. The predictive value of the 22-gene signature was independent of the conventional clinical variables. Gene set enrichment analysis revealed that the expression signatures of hypoxia phenotype and stem-like traits were significantly enriched in the low-score subgroup. In addition, the low-score subgroup was associated with the gene sets involved in resistance to anticancer drugs. In conclusion, hypoxia- or stem-like gene expression properties are associated with chemotherapy-resistance in HNSCC. The 22-gene signature may be useful as a predictive marker to help distinguish patients who will benefit from postoperative concurrent chemoradiotherapy.