m7G-related genes predict prognosis and affect the immune microenvironment and drug sensitivity in osteosarcoma

Zili Lin; Ziyi Wu; Yuhao Yuan; Wei Zhong; Wei Luo

doi:10.3389/fphar.2023.1158775

m7G-related genes predict prognosis and affect the immune microenvironment and drug sensitivity in osteosarcoma

Front Pharmacol. 2023 Aug 16:14:1158775. doi: 10.3389/fphar.2023.1158775. eCollection 2023.

Authors

Zili Lin^{1

2}, Ziyi Wu³, Yuhao Yuan^{1

2}, Wei Zhong^{1

2}, Wei Luo^{1

2}

Affiliations

¹ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
³ Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Osteosarcoma (OS), a primary malignant bone tumor, confronts therapeutic challenges rooted in multidrug resistance. Comprehensive understanding of disease occurrence and progression is imperative for advancing treatment strategies. m7G modification, an emerging post-transcriptional modification implicated in various diseases, may provide new insights to explore OS pathogenesis and progression. Methods: The m7G-related molecular landscape in OS was probed using diverse bioinformatics analyses, encompassing LASSO Cox regression, immune infiltration assessment, and drug sensitivity analysis. Furthermore, the therapeutic potential of AZD2014 for OS was investigated through cell apoptosis and cycle assays. Eventually, multivariate Cox analysis and experimental validations, were conducted to investigate the independent prognostic m7G-related genes. Results: A comprehensive m7G-related risk model incorporating eight signatures was established, with corresponding risk scores correlated with immune infiltration and drug sensitivity. Drug sensitivity analysis spotlighted AZD2014 as a potential therapeutic candidate for OS. Subsequent experiments corroborated AZD2014's capability to induce G1-phase cell cycle arrest and apoptosis in OS cells. Ultimately, multivariate Cox regression analysis unveiled the independent prognostic importance of CYFIP1 and EIF4A1, differential expressions of which were validated at histological and cytological levels. Conclusion: This study furnishes a profound understanding of the contribution of m7G-related genes to the pathogenesis of OS. The discerned therapeutic potential of AZD2014, in conjunction with the identification of CYFIP1 and EIF4A1 as independent risk factors, opens novel vistas for the treatment of OS.

Keywords: AZD2014; drug sensitivity; immune infiltration; m7G; osteosarcoma; prognosis.

Grants and funding

This work was funded under the special funds for the construction of innovative provinces in Hunan Province (grant no. 2020RC3058) and the Provincial Science Foundation of Hunan (grant no. 2022JJ30075).