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Treatment Resistant Cancers

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High-Throughput Transcriptomics Identifies Chemoresistance-Associated Gene Expression Signatures in Human

Glenys Mai Shia Khor^1,2, Sara Haghani¹, Tiffany Rui En Tan¹

¹Cancer Discovery Hub, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore 168583, Singapore.

International Journal of Molecular Sciences

|October 16, 2024

Summary

This study identifies SPP1 as a key biomarker for chemoresistance in angiosarcoma, a rare and aggressive cancer. SPP1 overexpression is linked to poor prognosis and reduced sensitivity to chemotherapy, suggesting new therapeutic targets.

Keywords:

angiosarcoma chemoresistance immune-oncology secreted phosphoprotein 1 whole transcriptome sequencing

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Area of Science:

Oncology
Molecular Biology
Genomics

Background:

Angiosarcomas are aggressive endothelial cancers with poor prognosis and chemoresistance.
Identifying biomarkers for chemoresistance is crucial for improving angiosarcoma treatment outcomes.

Purpose of the Study:

To identify transcriptomic biomarkers associated with chemotherapy resistance in angiosarcoma.
To investigate the role of SPP1 as a potential biomarker for chemoresistance and prognosis.

Main Methods:

Analysis of gene expression profiling (NanoString, RNA-seq) and immunohistochemistry in 72 Asian angiosarcoma cases.
Correlation of gene expression with clinical data, chemotherapy response, and cell line sensitivity.
Investigation of SPP1 expression in tumor tissues versus normal adjacent compartments.

Main Results:

Significant overexpression of SPP1, CXCL13, CD48, and CLEC5A in chemoresistant angiosarcomas.
SPP1 expression was higher in tumor tissues and correlated positively with protein levels.
Increased SPP1 expression associated with poorer survival, epithelioid histology, higher tumor grade, and reduced chemosensitivity.

Conclusions:

SPP1 overexpression is a potential biomarker for chemoresistance and poor prognosis in angiosarcoma.
Further research is needed to elucidate the precise mechanisms of SPP1 in angiosarcoma pathogenesis.