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Multi-omics profiling reveal cells with novel oncogenic cluster, TRAP1 low /CAMSAP3 low , emerge more aggressive behavior and poor-prognosis in early-stage endometrial cancer.
- Source :
-
Molecular cancer [Mol Cancer] 2024 Jun 17; Vol. 23 (1), pp. 127. Date of Electronic Publication: 2024 Jun 17. - Publication Year :
- 2024
-
Abstract
- The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous tissues from 24 early-stage endometrioid EC patients with different survival outcomes, 13 differentially expressed proteins were screen out while 2 proteins enriched in p53 signaling pathway were further identified by single-cell transcriptome (scRNA-seq). Interestingly, tumor necrosis factor type-1 receptor-associated protein (TRAP1) and calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) were found to be significantly downregulated in the specific cell cluster. Expectedly, the signature genes of TRAP1 <superscript>low</superscript> /CAMSAP3 <superscript>low</superscript> cluster included classical oncogenes. Moreover, close cellular interactions were observed between myeloid cells and the TRAP1 <superscript>low</superscript> /CAMSAP3 <superscript>low</superscript> cluster after systematically elucidating their relationship with tumor microenvironment (TME). The expression of TRAP1 and CAMSAP3 was verified by immunohistochemistry. Thus, a novel prediction model combining TRAP1, CAMSAP3 and TP53 was construct by multi-omics. Compared with the area under the curve, it demonstrated a significantly improvemrnt in the diagnostic efficacy in EC patients from TCGA bank. In conclusion, this work improved the current knowledge regarding the prognosis of early-stage EC through proteomics and scRNA-seq. These findings may lead to improvements in precise risk stratification of early-stage EC patients.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Female
Prognosis
Tumor Microenvironment genetics
Gene Expression Profiling
Middle Aged
Transcriptome
Multiomics
HSP90 Heat-Shock Proteins
Endometrial Neoplasms genetics
Endometrial Neoplasms pathology
Endometrial Neoplasms metabolism
Endometrial Neoplasms mortality
Biomarkers, Tumor genetics
Proteomics methods
Gene Expression Regulation, Neoplastic
Neoplasm Staging
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 38880903
- Full Text :
- https://doi.org/10.1186/s12943-024-02039-2