Clinical-proteomic classification and precision treatment strategy of chordoma

Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.

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Publication Details

Journal
Cell Reports Medicine
Published
2024-10-01
DOI
https://doi.org/10.1016/j.xcrm.2024.101757
Citations
6
Primary Topic
Bone Tumor Diagnosis and Treatments
Type
article
Field-Weighted Citation Impact
2.82

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article

Clinical-proteomic classification and precision treatment strategy of chordoma

Ping Wang, Jinbo Hu, Tong Meng, Jiali Jin et al.
6 citations
Cell Reports Medicine
Bone Tumor Diagnosis and Treatments
2.82
article

Clinical-proteomic classification and precision treatment strategy of chordoma

Ping Wang, Jinbo Hu, Tong Meng, Jiali Jin, Zhengdong Cai, Dianwen Song, Zhengyan Chang, Cong Jiang, Wei Sun, Tong Su, Jianxuan Gao, Xiaowen Xu, Zhou Wang, Jun Lin, Wenxuan Yin, Huabin Yin
article en
6 citations

Abstract

Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.

Cell Reports MedicineVol. 5(10)
Tongji University (CN), Renji Hospital (CN), XinHua Hospital (CN), Ruijin Hospital (CN), Shanghai Chest Hospital (CN), Shanghai Changzheng Hospital (CN), Shanghai Cancer Institute (CN), Shanghai Tenth People's Hospital (CN), Shanghai First People's Hospital (CN), Tongji Hospital (CN)
Chordoma Foundation, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Shanghai Rising-Star Program
Good health and well-being
Openalex Percentile: Top 9%
Bone Tumor Diagnosis and Treatments
2.82
DOIOpen Access PDFOpenAlex
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