Methylation-based reclassification and risk stratification of skull-base chordomas

作者：Xulei Huo, Teng-Xian Guo, Ke Wang, Bo-Han Yao, Da Li, Huan Li, Wei Chen, Liang Wang, Zhen Wu · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.960005 · 被引用次数：24 · 研究领域：Bone Tumor Diagnosis and Treatments、Sarcoma Diagnosis and Treatment、Chromatin Remodeling and Cancer

Background: Skull-base chordomas are rare malignant bone cancers originating from the remnant of the notochord. Survival is variable, and clinical or molecular factors cannot reliably predict their outcomes. This study therefore identified epigenetic subtypes that defined new chordoma epigenetic profiles and their corresponding characteristics. Methods: Methylation profiles of 46 chordoma-resected neoplasms between 2008 and 2014, along with clinical information, were collected. K-means consensus clustering and principal component analysis were used to identify and validate the clusters. Single-sample gene set enrichment analysis, methylCIBERSORT algorithm, and copy number analysis were used to identify the characteristics of the clusters. Results: Unsupervised clustering analysis confirmed two clusters with a progression-free survival difference. Gene set enrichment analysis indicated that the early and late estrogen response pathways and the hypoxia pathway were activated whereas the inflammatory and interferon gamma responses were suppressed. Forty-six potential therapeutic targets corresponding to differentially methylated sites were identified from chordoma patients. Subgroups with a worse outcome were characterized by low immune cell infiltration, higher tumor purity, and higher stemness indices. Moreover, copy number amplifications mostly occurred in cluster 1 tumors and the high-risk group. Additionally, the presence of a CCNE1 deletion was exclusively found in the gro...