颅底脊索瘤的蛋白质基因组学特征。

Proteogenomic characterization of skull-base chordoma.

机构信息

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.

National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Nat Commun. 2024 Sep 27;15(1):8338. doi: 10.1038/s41467-024-52285-7.

DOI:10.1038/s41467-024-52285-7

PMID:39333076

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436687/

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.

摘要

颅底脊索瘤是一种罕见的侵袭性骨癌，复发率较高。尽管基因组研究取得了进展，但它的分子特征和有效治疗方法仍不清楚。在这里，我们对 187 例颅底脊索瘤肿瘤进行了整合基因组学、转录组学、蛋白质组学和磷酸化蛋白质组学分析。在我们的研究中，染色体不稳定性被确定为预后预测因子和潜在的治疗靶点。多组学数据揭示了染色体不稳定性的下游效应，其中 RPRD1B 是放疗抵抗患者的一个潜在靶点。与染色体不稳定和上调的线粒体功能相关的 1q 染色体增益导致更差的临床结果。免疫亚群分析确定了与 9p/10q 缺失和免疫逃逸相关的免疫冷亚型。基于蛋白质组学的分类揭示了具有高染色体不稳定性和免疫冷特征的亚型（P-II 和 P-III），其中 P-II 肿瘤表现出侵袭性增加。这些在 17 对配对样本中得到证实的发现，为颅底脊索瘤的生物学和治疗提供了新的见解。