Table11_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.XLSX
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.
History
References
- https://doi.org//10.1186/s13059-017-1349-1
- https://doi.org//10.3390/ijms20092241
- https://doi.org//10.1186/s13059-016-1070-5
- https://doi.org//10.3322/caac.21492
- https://doi.org//10.1016/j.critrevonc.2017.01.017
- https://doi.org//10.1093/bioinformatics/btz006
- https://doi.org//10.1016/j.canlet.2020.04.007
- https://doi.org//10.1038/s41416-019-0394-9
- https://doi.org//10.1186/s13073-019-0638-6
- https://doi.org//10.3390/cancers12010252
- https://doi.org//10.1093/neuonc/now132
- https://doi.org//10.1016/j.jaad.2017.05.047
- https://doi.org//10.1038/s41598-019-44991-w
- https://doi.org//10.1593/neo.05733
- https://doi.org//10.1016/j.cell.2011.02.013
- https://doi.org//10.1186/s40425-019-0726-6
- https://doi.org//10.21873/cgp.20236
- https://doi.org//10.1016/j.radonc.2018.05.003
- https://doi.org//10.4143/crt.2019.440
- https://doi.org//10.1016/j.radonc.2017.05.009
- https://doi.org//10.3892/or.2016.5261
- https://doi.org//10.1210/clinem/dgaa316
- https://doi.org//10.1186/1471-2164-13-348
- https://doi.org//10.3892/or_00000373
- https://doi.org//10.1158/1078-0432.ccr-19-3211
- https://doi.org//10.3389/fcell.2020.00425
- https://doi.org//10.18632/genesandcancer.54
- https://doi.org//10.1038/nrc2044
- https://doi.org//10.1097/pai.0000000000000705
- https://doi.org//10.1093/nar/gkaa407
- https://doi.org//10.1038/s41388-020-01636-x
- https://doi.org//10.1101/cshperspect.a026831
- https://doi.org//10.1371/journal.pone.0142656
- https://doi.org//10.3389/fonc.2021.657002
- https://doi.org//10.1186/s40463-018-0302-y
- https://doi.org//10.1186/s13045-018-0647-8
- https://doi.org//10.7150/jca.27199
- https://doi.org//10.1093/nar/gks042
- https://doi.org//10.18632/oncotarget.17547
- https://doi.org//10.1093/bib/bbw112
- https://doi.org//10.1155/2009/359457
- https://doi.org//10.1634/theoncologist.2014-0422
- https://doi.org//10.7554/eLife.26476
- https://doi.org//10.2147/dddt.s140687
- https://doi.org//10.1093/nar/gkv007
- https://doi.org//10.1007/s10147-020-01666-1
- https://doi.org//10.2217/fon-2020-0385
- https://doi.org//10.1016/j.ejca.2017.08.001
- https://doi.org//10.1016/j.cell.2017.10.049
- https://doi.org//10.1186/s13046-018-0758-7
- https://doi.org//10.1073/pnas.0406351101
- https://doi.org//10.1056/nejmoa1200690
- https://doi.org//10.1056/nejm199301213280306
- https://doi.org//10.3389/fphar.2018.00185
- https://doi.org//10.3389/fonc.2021.639724
- https://doi.org//10.18632/oncotarget.10788
- https://doi.org//10.1158/1078-0432.ccr-18-1481
- https://doi.org//10.18632/oncotarget.23580
- https://doi.org//10.1186/s12885-018-5243-3