Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma

Dafu Chen; Ben Wan; Yuning Cheng; Yuwen Luo; Xueshan Bai; Jianxun Guo; Guangping Li; Tao Jin; Jingjun Nie; Weifeng Liu; Renxian Wang

doi:10.7717/peerj.15814

Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma

PeerJ. 2023 Aug 30:11:e15814. doi: 10.7717/peerj.15814. eCollection 2023.

Authors

Dafu Chen^#¹, Ben Wan^#^{1

2}, Yuning Cheng¹, Yuwen Luo¹, Xueshan Bai³, Jianxun Guo¹, Guangping Li¹, Tao Jin⁴, Jingjun Nie¹, Weifeng Liu⁴, Renxian Wang^{1

5}

Affiliations

¹ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
² Department of Oral and Maxillofacial Surgery, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
³ Cranio-Maxillo-Facial Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁴ Depatment of Orthopaedic Oncology Surgery, National Center for Orthopaedics, Beijing JiShuiTan Hospital, Capital Medical University, Beijing, China.
⁵ JST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.

^# Contributed equally.

Abstract

Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.

Keywords: Carboxypeptidase E; Differentially; Expressed genes; Osteosarcoma; Prognostic genes; Single-cell genomics; mRNA microarray.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Biomarkers
Bone Neoplasms* / genetics
Carboxypeptidase H / genetics
Child
Humans
Osteosarcoma* / genetics
Prognosis

Substances

Carboxypeptidase H
Biomarkers

Grants and funding

This work was supported by the National Natural Science Foundation of China (52173275, 51973021, 51932002, 51903013); the Beijing Municipal Health Commission (BJRITO-RDP-2023, PXM 2020_026275_000002, BMHC-2021-6, BMHC-2019-9); and the Beijing Jishuitan Hospital Nova Program (XKXX202115, XKXX202114). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.