Combination of Radiosensitivity Gene Signature and PD-L1 Status Predicts Clinical Outcome of Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: A Study Based on The Cancer Genome Atlas Dataset.
Front Mol Biosci
; 8: 775562, 2021.
Article
en En
| MEDLINE
| ID: mdl-34970597
ABSTRACT
Aim:
The aim of our study was to investigate the potential predictive value of the combination of radiosensitivity gene signature and PD-L1 expression for the prognosis of locally advanced head and neck squamous cell carcinoma (HNSCC).Methods:
The cohort was selected from The Cancer Genome Atlas (TCGA) and classified into the radiosensitive (RS) group and radioresistant (RR) group by a radiosensitivity-related gene signature. The cohort was also grouped as PD-L1-high or PD-L1-low based on PD-L1 mRNA expression. The least absolute shrinkage and selection operator (lasso)-based Cox model was used to select hub survival genes. An independent validation cohort was obtained from the Gene Expression Omnibus (GEO) database.Results:
We selected 288 locally advanced HNSCC patients from TCGA. The Kaplan-Meier method found that the RR and PD-L1-high group had a worse survival than others (p = 0.033). The differentially expressed gene (DEG) analysis identified 553 upregulated genes and 486 downregulated genes (p < 0.05, fold change >2) between the RR and PD-L1-high group and others. The univariate Cox analysis of each DEG and subsequent lasso-based Cox model revealed five hub survival genes (POU4F1, IL34, HLF, CBS, and RNF165). A further hub survival gene-based risk score model was constructed, which was validated by an external cohort. We observed that a higher risk score predicted a worse prognosis (p = 0.0013). The area under the receiver operating characteristic curve (AUC) plots showed that this risk score model had good prediction value (1-year AUC = 0.684, 2-year AUC = 0.702, and 3-year AUC = 0.688). Five different deconvolution methods all showed that the B cells were lower in the RR and PD-L1-high group (p < 0.05). Finally, connectivity mapping analysis showed that the histone deacetylase (HDAC) inhibitor trichostatin A might have the potential to reverse the phenotype of RR and PD-L1-high in locally advanced HNSCC (p < 0.05, false discovery rate <0.1).Conclusion:
The combination of 31-gene signature and the PD-L1 mRNA expression had a potential predictive value for the prognosis of locally advanced HNSCC who had RT. The B cells were lower in the RR and PD-L1-high group. The identified risk gene signature of locally advanced HNSCC and the potential therapeutic drug trichostatin A for the RR and PD-L1-high group are worth being further studied in a prospective homogenous cohort.
Texto completo:
1
Bases de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Front Mol Biosci
Año:
2021
Tipo del documento:
Article
País de afiliación:
China