Abstract
Angiosarcomas, clinically aggressive cancers of endothelial origin, are a rare subtype of soft-tissue sarcomas characterized by resistance to chemotherapy and dismal prognosis. In this study, we aim to identify the transcriptomic biomarkers of chemoresistance in angiosarcoma. We examined 72 cases of Asian angiosarcomas, including 35 cases treated with palliative chemotherapy, integrating information from NanoString gene expression profiling, whole transcriptome profiling (RNA-seq), immunohistochemistry, cell line assays, and clinicopathological data. In the chemoresistant cohort (defined as stable disease or progression), we observed the significant overexpression of genes, including SPP1 (log2foldchange 3.49, adj. p = 0.0112), CXCL13, CD48, and CLEC5A, accompanied by the significant enrichment of myeloid compartment and cytokine and chemokine signaling pathways, as well as neutrophils and macrophages. RNA-seq data revealed higher SPP1 expression (p = 0.0008) in tumor tissues over adjacent normal compartments. Immunohistochemistry showed a significant moderate positive correlation between SPP1 protein and gene expression (r = 0.7016; p < 0.00110), while higher SPP1 protein expression correlated with lower chemotherapeutic sensitivity in patient-derived angiosarcoma cell lines MOLAS and ISOHAS. In addition, SPP1 mRNA overexpression positively correlated with epithelioid histology (p = 0.007), higher tumor grade (p = 0.0023), non-head and neck location (p = 0.0576), and poorer overall survival outcomes (HR 1.84, 95% CI 1.07–3.18, p = 0.0288). There was no association with tumor mutational burden, tumor inflammation signature, the presence of human herpesvirus-7, ultraviolet exposure signature, and metastatic state at diagnosis. In conclusion, SPP1 overexpression may be a biomarker of chemoresistance and poor prognosis in angiosarcoma. Further investigation is needed to uncover the precise roles and underlying mechanisms of SPP1.
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MDPI and ACS Style
Khor, G.M.S.; Haghani, S.; Tan, T.R.E.; Lee, E.C.Y.; Kannan, B.; Lim, B.Y.; Lee, J.Y.; Guo, Z.; Ko, T.K.; Chan, J.Y.
High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human Angiosarcoma. Int. J. Mol. Sci. 2024, 25, 10863.
https://doi.org/10.3390/ijms251910863
AMA Style
Khor GMS, Haghani S, Tan TRE, Lee ECY, Kannan B, Lim BY, Lee JY, Guo Z, Ko TK, Chan JY.
High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human Angiosarcoma. International Journal of Molecular Sciences. 2024; 25(19):10863.
https://doi.org/10.3390/ijms251910863
Chicago/Turabian Style
Khor, Glenys Mai Shia, Sara Haghani, Tiffany Rui En Tan, Elizabeth Chun Yong Lee, Bavani Kannan, Boon Yee Lim, Jing Yi Lee, Zexi Guo, Tun Kiat Ko, and Jason Yongsheng Chan.
2024. "High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human Angiosarcoma" International Journal of Molecular Sciences 25, no. 19: 10863.
https://doi.org/10.3390/ijms251910863
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