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RNA-seq and Single-Cell Transcriptome Analyses of TRAIL Receptors Gene Expression in Human Osteosarcoma Cells and
Wenyu Feng1, Haiyingjie Lin2, Emel Rothzerg2
1Department of Orthopaedics, the Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
Osteosarcoma (OS) is the most common primary cancer in the skeletal system, characterized by a high incidence of lung metastasis, local recurrence and death. Systemic treatment of this aggressive cancer has not improved significantly since the introduction of chemotherapy regimens, underscoring a critical need for new treatment strategies. TRAIL receptors have long been proposed to be therapeutic targets for cancer treatment, but their role in osteosarcoma remains unclear. In this study, we investigated the expression profile of four TRAIL receptors in human OS cells using total RNA-seq and single-cell RNA-seq (scRNA-seq). The results revealed that TNFRSF10B and TNFRSF10D but not TNFRSF10A and TNFRSF10C are differentially expressed in human OS cells as compared to normal cells. At the single cell level by scRNA-seq analyses, TNFRSF10B, TNFRSF10D, TNFRSF10A and TNFRSF10C are most abundantly expressed in endothelial cells of OS tissues among nine distinct cell clusters. Notably, in osteoblastic OS cells, TNFRSF10B is most abundantly expressed, followed by TNFRSF10D, TNFRSF10A and TNFRSF10C. Similarly, in an OS cell line U2-OS using RNA-seq, TNFRSF10B is most abundantly expressed, followed by TNFRSF10D, TNFRSF10A and TNFRSF10C. According to the TARGET online database, poor patient outcomes were associated with low expression of TNFRSF10C. These results could provide a new perspective to design novel therapeutic targets of TRAIL receptors for the diagnosis, prognosis and treatment of OS and other cancers.
Insights
This study identifies key TRAIL receptor expression patterns in osteosarcoma (OS). TNFRSF10B and TNFRSF10D are differentially expressed, offering potential new therapeutic targets for this aggressive bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Osteosarcoma (OS) is a primary bone cancer with poor prognosis, often involving metastasis and recurrence.
- Current systemic treatments, including chemotherapy, have limited efficacy, necessitating novel therapeutic strategies.
- The role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) receptors in OS pathogenesis and treatment remains largely unexplored.
Purpose of the Study:
- To investigate the expression profile of four TRAIL receptors (TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D) in human osteosarcoma cells.
- To determine the differential expression of TRAIL receptors in OS cells compared to normal cells.
- To explore the potential of TRAIL receptors as therapeutic targets for osteosarcoma.
Main Methods:
- Total RNA sequencing (RNA-seq) was performed on human OS cells.
- Single-cell RNA sequencing (scRNA-seq) was utilized to analyze TRAIL receptor expression at the cellular level.
- Expression data was analyzed in conjunction with the TARGET online database for patient outcome correlation.
Main Results:
- TNFRSF10B and TNFRSF10D showed differential expression in human OS cells compared to normal cells.
- scRNA-seq revealed abundant expression of all four TRAIL receptors in endothelial cells within OS tissues.
- Osteoblastic OS cells and the U2-OS cell line predominantly expressed TNFRSF10B, followed by TNFRSF10D, TNFRSF10A, and TNFRSF10C.
- Low expression of TNFRSF10C correlated with poor patient outcomes in the TARGET database.
Conclusions:
- TNFRSF10B and TNFRSF10D are key TRAIL receptors with differential expression in osteosarcoma.
- TRAIL receptor expression varies across different cell types within OS, with endothelial cells and osteoblastic cells showing distinct patterns.
- TNFRSF10C expression may serve as a prognostic biomarker for osteosarcoma patients.
- These findings provide a novel perspective for developing TRAIL receptor-targeted therapies for osteosarcoma diagnosis, prognosis, and treatment.
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