DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma.
Silvia PomellaMatteo CassandriOmbretta MelaiuFrancesco MaramponMarco GargariVincenzo CampanellaRossella RotaGiovanni BarillariPublished in: International journal of molecular sciences (2023)
Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1 , CCNB2 , CDK2 , CDK4 , CHECK1 , E2F1 , FANCD2 , and PRKDC ) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy.
Keyphrases
- rna seq
- single cell
- dna damage response
- genome wide
- genome wide identification
- high frequency
- electronic health record
- gene expression
- dna damage
- bioinformatics analysis
- copy number
- dna repair
- poor prognosis
- big data
- dna methylation
- papillary thyroid
- end stage renal disease
- genome wide analysis
- transcranial magnetic stimulation
- endothelial cells
- ejection fraction
- chronic kidney disease
- emergency department
- multiple sclerosis
- squamous cell
- stem cells
- early stage
- squamous cell carcinoma
- data analysis
- risk assessment
- peritoneal dialysis
- long non coding rna
- quality improvement
- human health
- locally advanced
- case report
- childhood cancer
- artificial intelligence
- lymph node metastasis
- adverse drug
- cell therapy