Human Gene Set: SU_HO_CONV_CENT_CHONDROSARCOMA_C5_CHON2


Standard name SU_HO_CONV_CENT_CHONDROSARCOMA_C5_CHON2
Systematic name M49194
Brief description Expressed lower levels of cartilaginous matrix genes and elevated levels of genes involved in the cellular response to ER stress, namely, DDIT3, HSPA5, and ATF5. Low-grade and medium-grade samples contained Chon2 and Chon1 clusters. Chon1 and Chon2 clusters represent early malignant transformation involving activation of the ER stress pathway. The Chon2 cluster is a marker for the malignant transformation of differentiated tumours (consisting of Ben, Low, and Med). Chon2 cluster markers were enriched in response to ER stress (e.g., DDIT3, HSPA5, and TRIB3). The ER stress response identified in cartilage neoplasm appeared to play a role in the pathological process of tumorigenesis but not in normal skeletal development. The Chon2 cluster accumulated an additional copy number gain at chromosome 19. Thirty-three genes, including UBE2S and TRIM28, showed significant copy number gain at this region. The Chon2 signature score was increased along with tumour grades.
Full description or abstract The transformation of benign lesions to malignant tumours is a crucial aspect of understanding chondrosarcomas, which are malignant cartilage tumours that could develop from benign chondroid lesions. However, the process of malignant transformation for chondroid lesions remains poorly understood, and no reliable markers are available to aid clinical decision-making. To address this issue, we conducted a study analysing 11 primary cartilage tumours and controls using single-cell RNA sequencing. By creating a single-cell atlas, we were able to identify the role of endoplasmic reticulum (ER) stress in the malignant transformation of conventional central chondrosarcomas (CCCS). Our research revealed that lower levels of ER stress promote chondrosarcoma growth in a patient-derived xenograft mouse model, while intensive ER stress reduces primary chondrosarcoma cell viability. Furthermore, we discovered that the NF-?B pathway alleviates ER stress-induced apoptosis during chondrosarcoma progression. Our single-cell signatures and large public data support the use of key ER stress regulators, such as DNA Damage Inducible Transcript 3 (DDIT3; also known as CHOP), as malignant markers for overall patient survival. Ultimately, our study highlights the significant role that ER stress plays in the malignant transformation of cartilaginous tumours and provides a valuable resource for future diagnostic markers and therapeutic strategies.
Collection C8: Cell Type Signature
Source publication Pubmed 38267611   Authors: Su Z,Ho JWK,Yau RCH,Lam YL,Shek TWH,Yeung MCF,Chen H,Oreffo ROC,Cheah KSE,Cheung KSC
Exact source 42003_2024_5790_MOESM6_ESM Supplementary Data 3, Sheet 1. Clusters. Cluster 5. cluster.name Chon2
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External links https://www.nature.com/articles/s42003-024-05790-w
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Source species Homo sapiens
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