Identification of genetic and epigenetic biomarkers associated with cisplatin and radiotherapy response in head and neck squamous cell carcinoma cell lines

Background Recent advances in next-generation sequencing and high-throughput technologies have led to new insights in therapeutic mechanisms and enabled the discovery of novel genetic and epigenetic markers in head and neck cancer (HNSCC). Despite this progress, no biomarker for guiding treatment has yet been implemented in clinical practice for head and neck cancer, for example for predicting treatment response and enabling personalized therapy. This study aims to identify potential genetic and epigenetic biomarkers for guiding the treatment of HNSCC, by comparing cisplatin- and radiotherapy resistant versus sensitive cell lines. Methods We analyzed 61 HNSCC cell lines with previously characterized sensitivity to cisplatin and radiotherapy using Genotyping by Sequencing coupled with methylated DNA Immunoprecipitation (GBS-MeDIP). This method simultaneously tests for genetic and methylomic modifications in a reduced genomic fraction, allowing efficient identification of putative biomarkers. Results We identified 21 single-nucleotide polymorphisms (SNPs) and 4 differentially methylated regions (DMRs) which were significantly associated with treatment response to either cisplatin or radiotherapy. Many of these SNPs and DMRs are in genomic regions previously shown to be relevant for cancer treatment resistance. Conclusions Our results identified 21 SNPs and 4 DMRs that could serve as predictive biomarkers for cisplatin and radiotherapy response in HNSCC, highlighting their potential for personalized treatment strategies and improved clinical outcomes. Further studies are required to determine whether our findings are associated with the modulation of gene expression in therapy-resistant cell lines, to better understand the underlying mechanisms.