Integrated multi-omics analysis of post-translational modifications in head and neck squamous cell carcinoma: elucidating x-ray and carbon ion irradiation effects.

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma (HNSCC) exhibits heterogeneous responses to radiotherapy; however, the underlying multi-omics regulatory networks remain poorly characterized. This study elucidated the distinct post-translational modification (PTM) landscapes induced by X-ray and carbon-ion irradiation.

METHODS

Using integrated proteomics, phosphoproteomics, and acetylomics, we systematically profiled PTMs in HSC-3 cells at 30 min post-irradiation with X-ray (8 Gy) or carbon ions (4 GyE). Computational analyses included functional annotation, kinase activity prediction, and PTM crosstalk mapping.

RESULTS

Carbon ions induced 21% more phosphosites (2,781 vs. 2,301) and 61% more acetyl sites (3,324 vs. 2,070) than X-ray, demonstrating broader PTM reprogramming. Notably, carbon ion-induced histone hypoacetylation (H2AZ1K8/K5, H3C1K28/K24, and H4C1K92) and hyperphosphorylation (H1-10S2 and H3C1T119) potentially alter chromatin accessibility. Functional enrichment analyses revealed the activation of the non-homologous end-joining (NHEJ) pathway and coordinated upregulation of antigen-presenting machinery (such as CD274, TAP2, HLA-A, and PSMB8) through PTM remodeling. Distinct PTM signatures in RNA splicing factors implicate alternative splicing in radiation response. Kinase activity profiling revealed ATM hyperactivation and CDK suppression in the carbon ion group.

CONCLUSIONS

Carbon ion irradiation drives distinct PTM-mediated immunomodulatory and DNA damage-response networks, providing a mechanistic rationale for combining carbon ion radiotherapy with immunotherapy. Future studies should validate the PTM-associated targets to improve HNSCC treatment.