Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.
Immune gene
Metastasis
Soft tissue sarcoma
Transcription factor
Tumor-infiltrating immune cells
Journal
Cancer cell international
ISSN: 1475-2867
Titre abrégé: Cancer Cell Int
Pays: England
ID NLM: 101139795
Informations de publication
Date de publication:
04 Jan 2021
04 Jan 2021
Historique:
received:
29
03
2020
accepted:
29
10
2020
entrez:
5
1
2021
pubmed:
6
1
2021
medline:
6
1
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 33397394
doi: 10.1186/s12935-020-01632-x
pii: 10.1186/s12935-020-01632-x
pmc: PMC7784354
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3Subventions
Organisme : National Natural Science Foundation of China
ID : 81702659
Organisme : National Natural Science Foundation of China
ID : 81772856
Organisme : National Natural Science Foundation of China
ID : 82073207
Organisme : Youth Fund of Shanghai Municipal Health Planning Commission
ID : 20174Y0117
Organisme : Henan medical science and technology research project
ID : 201602031
Organisme : Interdisciplinary Program of Shanghai Jiao Tong University
ID : YG2017MS26
Organisme : Shanghai Talent Development Fund
ID : 2018094
Organisme : Key project of provincial and ministerial co-construction of Henan Medical Science and Technology
ID : 2020040
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