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Single-cell and spatial transcriptomics reveal post-translational modifications in osteosarcoma progression and tumor

Yue Cui1, Yue Wu1, Dongyu Jiang1

  • 1The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China.

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Post-translational modifications (PTMs) are key in osteosarcoma. A new gene signature (CMDPTMS) predicts outcomes and immunotherapy response, identifying potential therapeutic targets and confirming Vimentin

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Post-translational modifications (PTMs) play a role in osteosarcoma (OS) development, but their specific functions are not fully understood.
  • Understanding PTMs in OS is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

  • To investigate the role of PTMs in osteosarcoma pathogenesis using integrated multi-omics data.
  • To identify novel prognostic biomarkers and therapeutic targets for osteosarcoma.
  • To evaluate the potential of a new gene signature for predicting immunotherapy outcomes.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were used to classify and map tumor cells based on PTM scores.
  • A machine learning approach developed a consensus machine learning-derived post-translational modification gene signature (CMDPTMS).
  • Bulk transcriptomic data and laboratory experiments (Vimentin/VIM) were utilized for validation and functional analysis.

Main Results:

  • PTM scores were elevated in OS tumor cells, identifying distinct subtypes (PTMs high/low) with varying malignant characteristics and interactions with fibroblasts.
  • The CMDPTMS demonstrated strong prognostic predictive capability, with high-CMDPTMS linked to poor outcomes and reduced immunotherapy benefit.
  • Seven potential therapeutic drugs were identified for high-CMDPTMS patients, and Vimentin (VIM) was confirmed to inhibit OS cell growth and migration.

Conclusions:

  • The CMDPTMS serves as a potent tool for improving osteosarcoma prognosis prediction and optimizing immunotherapy strategies.
  • Integrated analysis of PTMs, transcriptomics, and spatial data provides novel insights into OS heterogeneity and therapeutic vulnerabilities.
  • Targeting Vimentin (VIM) may represent a potential therapeutic avenue for osteosarcoma treatment.