2. Academic Validation
  3. Construction of a DNA damage response-related signature for prognostication and therapeutic response prediction in head and neck squamous cell carcinoma

Construction of a DNA damage response-related signature for prognostication and therapeutic response prediction in head and neck squamous cell carcinoma

  • Arch Oral Biol. 2026 May:185:106557. doi: 10.1016/j.archoralbio.2026.106557.
Ruoyuan Li 1,  Xiaoxuan Bu 1,  Na Qi 1,  Pengfei Diao 1,  Yaping Wu 2,  Jie Cheng 3
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu 210029, PR China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Jiangsu 210029, PR China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Jiangsu 210029, PR China.
  • 2 Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu 210029, PR China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Jiangsu 210029, PR China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Jiangsu 210029, PR China. Electronic address: [email protected].
  • 3 Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu 210029, PR China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Jiangsu 210029, PR China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Jiangsu 210029, PR China. Electronic address: [email protected].
PMID: 41747404 DOI: 10.1016/j.archoralbio.2026.106557
Abstract

Objective: This study aimed to construct a novel signature utilizing DNA damage response-related genes (DRGs) for head and neck squamous cell carcinoma (HNSCC) prognostication and therapeutic prediction.

Design: A prognostic signature specific to HNSCC was developed using univariate COX regression, Kaplan-Meier survival analysis, and least absolute shrinkage and selection operator (LASSO)-penalized multivariate COX regression analyses. A nomogram incorporating this signature along with selected clinicopathological factors was obtained through multivariate COX regression. The effectiveness of this DRG signature in predicting immune status and chemotherapeutic or immunotherapeutic responses was evaluated. Gene function was assessed via a pharmacological approach in vitro.

Results: The 10-gene DRG signature/nomogram demonstrated well prognostic performance across various independent cohorts. Pharmacological inhibition of PLK1 from the DRG signature led to cell death and Apoptosis which were probably resulted from impaired DNA damage response. Higher DRG signature scores were negatively correlated with the abundance of tumor-infiltrating immune cells and linked to several chemotherapeutic drugs, radiotherapy, and immunotherapy sensitivities.

Conclusions: Our findings indicated that this novel DRG-derived signature/nomogram serves as a robust prognostic biomarker and viable therapeutic response predictor in HNSCC.

Keywords

DNA damage response; Head and neck squamous cell carcinoma; Prognosis; Therapeutic response.

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