Proteogenomic characterization of skull-base chordoma.

Nat Commun

Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200433, China.

Published: September 2024

AI Article Synopsis

  • Skull-base chordoma is a rare and aggressive bone cancer known for its high recurrence, and the study aims to understand its molecular characteristics and potential treatments through comprehensive analysis of 187 tumors.
  • The research identifies chromosome instability as a significant predictor of prognosis and a possible target for therapy, particularly highlighting RPRD1B in cases resistant to radiotherapy.
  • The study also characterizes tumor subtypes, revealing an immune cold subtype linked to poorer clinical outcomes, while showing that specific chromosomal gains and mitochondrial functions correlate with increased invasiveness in certain tumors.

Article Abstract

Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436687PMC
http://dx.doi.org/10.1038/s41467-024-52285-7DOI Listing

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