Abstract
BackgroundSoft 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.MethodsRNA-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.ResultsA 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.ConclusionsWe 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.
Highlights
Soft tissue sarcomas (STS) has a high rate of early metastasis
We hypothesized that down-regulated Lymphotoxin Beta (LTB) modulated by Paired Box 5 (PAX5) (TF) in STSs may have the capability of inducing cancer cell metastasis in patients with STS
In LinkedOmics, LTB was significantly correlated with PAX5 (P < 0.001, R = 0.31), Interleukin 1 Alpha (IL1A) (P = 0.008, R = 0.17), Interleukin 5 Receptor Subunit Alpha (IL5RA) (P < 0.001, R = 0.43), Interleukin 7 (IL7) (P < 0.001, R = 0.51), Lymphocyte Antigen 9 (LY9) (P < 0.001, R = 0.82), Signaling Lymphocytic Activation Molecule Family Member 7 (SLAMF7) (P < 0.001, R = 0.79), and Intercellular Adhesion Molecule 1 (ICAM1) (P < 0.001, R = 0.61) (Additional file 1: Figure S5)
Summary
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. Huang et al Cancer Cell Int (2021) 21:3 responsiveness to chemotherapy, surgery remains the standard treatment for patients with localized STS, but over 50% of patients may experience recurrence and metastasis after surgery [3]. Novel treatments, such as targeted therapies, and the identification of biomarkers for identifying early metastatic disease are desperately needed. Both molecular and cellular features have been shown to exert important influences on tumorigenesis and metastasis [4]. Metastasis-related TFs and tumourinfiltrating immune cells in STS have not been explored and need to be further analysed
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