Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients

Deliang Gong; Qingzhong Zhao; Jun Liu; Shibing Zhao; Chengfeng Yi; Jianwei Lv; Hang Yu; Erbao Bian; Dasheng Tian

doi:10.3389/fonc.2023.1169430

Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients

Front Oncol. 2023 Jun 5:13:1169430. doi: 10.3389/fonc.2023.1169430. eCollection 2023.

Authors

Deliang Gong^{1

2}, Qingzhong Zhao^{1

2}, Jun Liu^{1

2}, Shibing Zhao^{1

2}, Chengfeng Yi^{1

2}, Jianwei Lv^{1

2}, Hang Yu^{1

2}, Erbao Bian^{1

2}, Dasheng Tian^{1

2}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
² Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

Osteosarcoma is a primary malignant tumor found mainly in teenagers and young adults. Patients have very little long-term survival. MYC controls tumor initiation and progression by regulating the expression of its target genes; thus, constructing a risk signature of osteosarcoma MYC target gene set will benefit the evaluation of both treatment and prognosis. In this paper, we used GEO data to download the ChIP-seq data of MYC to obtain the MYC target gene. Then, a risk signature consisting of 10 MYC target genes was developed using Cox regression analysis. The signature indicates that patients in the high-risk group performed poorly. After that, we verified it in the GSE21257 dataset. In addition, the difference in tumor immune function among the low- and high-risk populations was compared by single sample gene enrichment analysis. Immunotherapy and prediction of response to the anticancer drug have shown that the risk signature of the MYC target gene set was positively correlated with immune checkpoint response and drug sensitivity. Functional analysis has demonstrated that these genes are enriched in malignant tumors. Finally, STX10 was selected for functional experimentation. STX10 silence has limited osteosarcoma cell migration, invasion, and proliferation. Therefore, these findings indicated that the MYC target gene set risk signature could be used as a potential therapeutic target and prognostic indicator in patients with osteosarcoma.

Keywords: MYC target gene set; STX10; osteosarcoma (OS); prognosis; risk signature.

Grants and funding

This research was funded by the Clinical Research and Cultivation Program of the Second Hospital of Anhui Medical University (2020LCZD05), the Translational Medicine Research Foundation of the Second Hospital of Anhui Medical University (2022ZHYJ13), the Key Projects of Natural Science Research in Colleges and Universities in Anhui Province (2022AH040102), and the Research Foundation of Anhui Institute of Translational Medicine (No. 2022zhyx-C49).