Single-Cell Transcriptome Analyses of Four Pain Related Genes in Osteosarcoma

TL;DR

This study explores the expression of four pain-related genes in osteosarcoma to better understand and treat pain in affected patients.

Contribution

The study identifies cell-type-specific expression patterns of four pain-related genes in osteosarcoma using single-cell RNA sequencing.

Findings

ARTN and NRTN are most highly expressed in osteoblastic OS cells.

GDNF shows peak expression in carcinoma-associated fibroblasts, and PSPN in endothelial cells.

All four genes display differential expression across 16 osteosarcoma cell lines.

Abstract

Osteosarcoma (OS) is a rare and complex form of cancer that mostly affects children and adolescents. Pain is a common symptom for patients in OS which causes significant unhappiness and persistent aches. To date, there is minimal knowledge on the mechanisms underlying OS induced pain and few treatment options for patients. Previous genetic studies have demonstrated that the panel of four genes, artemin (ARTN), persephin (PSPN), glial cell line-derived neurotropic factor (GDNF), and neurturin (NRTN) are associated with the regulation of pain processing in OS and analgesic responses.

In the present study, by utilising a scRNA-seq OS dataset, we aimed to measure the gene expression levels of four pain related genes, and compare them between the different cell types in human OS tissues and cell lines.

Within a complex and diverse range of cell types in OS tissues, including osteoblastic OS cells, carcinoma associated fibroblasts (CAFs), B cells, myeloid cells 1, myeloid cells 2, NK/T cells, plasmocytes, ARTN and NRTN genes had the highest expression in Osteoblastic OS cells, GDNF gene had a peak expression in carcinoma associated fibroblasts, and PSPN gene in endothelial cells. In addition, all four genes showed deferential pattern of expression in 16 OS cell lines.

Future studies should investigate the potential to target deferentially expressed pain-related genes in specific cell types of OS for therapeutic benefit to improve the quality of life for patients living with pain caused by OS.

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