Aims Osteosarcoma (OS) is the most common primary malignant tumour of the bone. However, further improvement in survival has not been achieved due to a lack of well-validated prognostic markers and more effective therapeutic agents. Recently, the c-Myc–phosphoribosyl pyrophosphate synthetase 2 (PRPS2) pathway has been shown to promote nucleic acid metabolism and cancer cell proliferation in malignant melanoma; phosphorylated mammalian target of rapamycin (p-mTOR) has been upregulated and an effective therapeutic target in OS. However, the p-mTOR–PRPS2 pathway has not been evaluated in OS.
Methods In this study, the expression level of PRPS2, p-mTOR and marker of proliferation (MKI-67) was observed in a cohort of specimens (including 236 OS cases and 56 control samples) using immunohistochemistry, and the association between expression level and clinicopathological characteristics of patients with OS was analysed.
Results PRPS2 protein level, which is related to tumour proliferation, was higher in OS cells (p=0.003) than in fibrous dysplasia, and the higher PRPS2 protein level was associated with a higher tumour recurrence (p=0.001). In addition, our statistical analysis confirmed that PRPS2 is a novel, independent prognostic indicator of OS. Finally, we found that the expression of p-mTOR was associated with the poor prognosis of patients with OS (p<0.05).
Conclusions PRPS2 is an independent prognostic marker and a potential therapeutic target for OS.
- bone tumours
- molecular pathology
Data availability statement
All data relevant to the study are included in the article or uploaded as supplemental information.
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YL, JY and JH are joint first authors.
Handling editor Dhirendra Govender.
Correction notice This article has been corrected since it was published. Junqing Yuan and Jin Huang are added as the co-first author. Wentao Huang is added as co-corresponding author.
Contributors Review of the pathology was undertaken by histopathologists HZ, WH, JH and JZ. YL provided many ideas in guiding the experiments and analysed the data. Samples were collected by JY. Survival information was obtained through telephone calls by JH and CC. Immunohistochemistry was completed by ML, JC, JT and TY. The manuscript was written by YL. The article was reviewed by HZ, YL, JH and WH.
Funding This work was supported by the Interdisciplinary Program of Shanghai Jiao Tong University (grant number YG2015QN12), Shanghai Science and Technology Development fund (grant number 19MC1911000) and the National Natural Science Foundation (grant number 81602099).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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