Essential genes analysis reveals small ribosomal subunit protein eS28 may be a prognostic factor and potential vulnerability in osteosarcoma

Chao Liang; Juan Zhou; Yongjie Wang; Yin Sun; Jin Zhou; Lan Shao; Zhichang Zhang; Wangjun Yan; Zhiyan Liu; Yang Dong

doi:10.1016/j.jbo.2023.100517

Essential genes analysis reveals small ribosomal subunit protein eS28 may be a prognostic factor and potential vulnerability in osteosarcoma

J Bone Oncol. 2023 Dec 15:44:100517. doi: 10.1016/j.jbo.2023.100517. eCollection 2024 Feb.

Authors

Chao Liang^{1

2}, Juan Zhou³, Yongjie Wang⁴, Yin Sun², Jin Zhou², Lan Shao², Zhichang Zhang², Wangjun Yan¹, Zhiyan Liu³, Yang Dong²

Affiliations

¹ Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
² Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, PR China.
³ Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, PR China.
⁴ Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China.

Abstract

Background: Osteosarcoma, the most common primary malignant bone tumor, is currently treated with surgery combined with chemotherapy, but the limited availability of targeted drugs contributes to a poor prognosis. Identifying effective therapeutic targets is crucial for improving the prognosis of osteosarcoma patients.

Methods: We screened the DepMap database to identify essential genes as potential therapeutic targets for osteosarcoma. Gene Set Enrichment Analysis (GSEA) was employed to elucidate the biological roles of these essential genes. Promising candidates were filtered through univariate and multivariate Cox analyses, as well as Kaplan-Meier survival analyses using the GSE21257-OSA and TARGET-OSA datasets. The functional role of the target gene was assessed through cell experiments. Additionally, an in situ nude mice model was established to observe the gene's function, and RNA sequencing was utilized to explore the underlying molecular mechanism.

Results: A total of 934 essential genes were identified based on their effects (Chronos) using the DepMap database. These genes were primarily enriched in the ribosome pathway according to GSEA analysis. Among them, 195 genes were associated with the ribosome pathway. Rps28, Rps7, and Rps25 were validated as promising candidates following univariate and multivariate Cox analyses of the TARGET-OSA and GSE21257-OSA datasets. Kaplan-Meier survival analyses indicated Rps28 represented an especially promising target, with high expression correlating with poor prognosis. Knockdown of small ribosomal subunit protein eS28, the protein of Rps28, inhibited proliferation, migration, and invasion in both in vitro and in vivo experiments. Silencing RPS28 affected the MAPK signaling pathway in osteosarcoma.

Conclusion: In summary, Rps28 has been identified as an essential gene for osteosarcoma cell survival and eS28 may serve as a potential vulnerability in osteosarcoma.

Keywords: CRISPR/Cas9 library; MAPK signal pathways; Osteosarcoma; RPS28; Ribosome biogenesis; eS28.