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Updated: Nov 23, 2025
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis
Runzhi Huang1,2, Zhiwei Zeng1, Penghui Yan1
1Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, 450052, China.
Background:
Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells.
Methods:
RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data.
Results:
A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P < 0.001, R = 0.829) and hematopoietic cell lineage pathway (P < 0.001, R = 0.375). The transcriptional regulatory pattern between PAX5 and LTB was validated by ChIP sequencing data.
Conclusions:
We hypothesized that down-regulated LTB (immune gene) modulated by PAX5 (TF) in STSs may have the capability of inducing cancer cell metastasis in patients with STS.
Insights
This study investigated metastasis mechanisms in soft tissue sarcomas (STS). Down-regulated LTB, modulated by PAX5, may drive cancer cell metastasis in STS patients.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Soft tissue sarcomas (STS) are characterized by a high incidence of early metastasis.
- Understanding the molecular mechanisms driving STS metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To identify metastasis-related genes and signaling pathways in STS.
- To uncover the role of tumor-infiltrating cells and differentially expressed genes in STS metastasis.
Main Methods:
- RNA-sequencing (RNA-seq) analysis of 261 STS samples from TCGA.
- Identification of metastasis-related immune genes and transcription factors (TFs).
- Construction of a metastasis prediction model and analysis of immune cell infiltration and KEGG pathways.
Main Results:
- 204 immune genes and 12 TFs were identified.
- A metastasis prediction model demonstrated high effectiveness (AUC=0.808).
- LTB was significantly correlated with PAX5 and the hematopoietic cell lineage pathway, with validation via ChIP sequencing.
Conclusions:
- Down-regulated LTB, modulated by PAX5, is hypothesized to promote cancer cell metastasis in STS.
- This finding provides insights into the molecular drivers of STS metastasis.
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