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. 2024 Dec 30;15(1):848.
doi: 10.1007/s12672-024-01689-4.

A novel histone acetylation-associated gene signature with prognostic value in Ewing sarcoma

Anshun Wu #  1 , Fayin Liu #  2 , Lei Zhou #  3 , Runyi Jiang  3 , Shangjiang Yu  4 , Zihuan Zhou  3 , Qi Zhang  3 , Qian Zhang  3 , Dongjie Jiang #  5 , Shaohui He #  6 , Haifeng Wei #  7   8
Affiliations

A novel histone acetylation-associated gene signature with prognostic value in Ewing sarcoma

Anshun Wu et al. Discov Oncol. .

Abstract

Histone acetylation is an important epigenetic modification, modulating the development of many tumors. However, the functions of most histone acetylation-related genes (HARGs) and their prognostic values in Ewing sarcoma (EWS) remain unclear. The current study aimed to investigate the prognostic values and potential functions of HARGs in EWS. After collecting EWS patients with mRNA sequencing data from the Gene Expression Omnibus (GEO) database and a list of HARGs from previous studies, Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to construct a prognostic gene signature based on HARGs. Then, four HARGs (TAF4, ATF2, HDAC2 and OGA) composed a formula to calculate risk score for each patient in the training cohort. Based on median risk score, all patients were classified into low- and high-risk group, and patients with high-risk score had a poor survival outcome (p < 0.001). The 1-, 2-,3- and 5-year AUC (0.853, 0.886,0.909and 0.833, respectively) showed the good ability of this signature to predict the prognoses of EWS patients. In addition, distinct functional enrichment and immune-related pathways were also observed in two risk groups. All results were validated in an external cohort from two dataset in GEO database. Moreover, it was found that silencing HDAC2 expression in EWS cells significantly suppressed the cell viability and migration capability. In conclusion, this is the first study to detect the prognostic values of HARGs in EWS patients, further developing a good prognostic signature based on HARGs, and HDAC2 might be an oncogene in the development of EWS.

Keywords: Ewing sarcoma; HDAC2; Histone acetylation; Prognostic signature.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The flowchart of this study
Fig. 2
Fig. 2
Identifying histone acetylation-related genes (HARGs) associated with the prognoses of Ewing sarcoma (EWS) patients. A The volcano plot of differently expressed genes (DEGs) in normal and EWS samples. B The intersection of DEGs and HARGs. C Univariate Cox regression determining 19 HARGs correlated with prognoses of EWS patients
Fig. 3
Fig. 3
Developing a prognostic signature based on four HARGs for EWS patients in the training cohort. A, B LASSO regression further selecting HARGs related to the prognoses of EWS patients. C Multivariate Cox regression identifying four HARGs to develop a prognostic signature. D The ROC to test the predictive ability of the constructed signature. E–H The KM curves of the four HARGs
Fig. 4
Fig. 4
The difference of low- and high-risk groups group in the training cohort. A–C The different survival outcomes of EWS patients. D The results of Gene Ontology (GO) enrichment based on DEGs in two risk groups. E The different immune-related pathways. F The significantly different immune checkpoints
Fig. 5
Fig. 5
Validating the developed HARGs signature in an external cohort. A–C The different prognoses of EWS patients in two risk groups. D Estimating the ability of the developed signature to predict survival outcomes of EWS patients. E–H The KM curves of the four HARGs
Fig. 6
Fig. 6
The difference of functional analyses in low- and high-risk group in the validation cohort. A The GO enrichment analyses. B The analyses of immune-related pathways. C The detection of differently expressed immune checkpoints
Fig. 7
Fig. 7
Exploring the influence of HDAC2 on the development of EWS cells. A The knockdown efficiency of HDAC2 after transfection in A673 and RD-ES cells. B The cell viability of A673 and RD-ES after silencing HDAC2
Fig. 8
Fig. 8
Exploring the influence of HDAC2 on the development of EWS cells. A The cell clonogenic assay of A673 and RD-ES after silencing HDAC2. B The migrated ability of A673 and RD-ES after silencing HDAC2
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References

    1. Osgood CL, Maloney N, Kidd CG, Kitchen-Goosen S, Segars L, Gebregiorgis M, et al. Identification of mithramycin analogues with improved targeting of the EWS-FLI1 transcription factor. Clin Cancer Res. 2016;22(16):4105–18. - PMC - PubMed
    1. Marchetto A, Ohmura S, Orth MF, Knott MML, Colombo MV, Arrigoni C, et al. Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma. Nat Commun. 2020;11(1):2423. - PMC - PubMed
    1. Jiang R, Hu J, Zhou H, Wei H, He S, Xiao J. A novel defined hypoxia-related gene signature for prognostic prediction of patients with ewing sarcoma. Front Genet. 2022;13: 908113. - PMC - PubMed
    1. Fleuren ED, Versleijen-Jonkers YM, van de Luijtgaarden AC, Molkenboer-Kuenen JD, Heskamp S, Roeffen MH, et al. Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507. Clin Cancer Res. 2011;17(24):7693–703. - PMC - PubMed
    1. Takahashi A, de Andrés MC, Hashimoto K, Itoi E, Oreffo RO. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthritis Cartil. 2015;23(11):1946–54. - PMC - PubMed

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