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pmid:38720884

Identifying specific TLS-associated genes as potential biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in soft tissue sarcoma.

Xiang-Xu Wang · Yun-Peng Liu · Yajie Lu · Li-Hong Wu · Jing-Yi Ren · Hongchen Ji · Xiaowen Wang · Hong-Mei Zhang

Frontiers in immunology · 2024 doi:10.3389/fimmu.2024.1372692

Paper

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Experiment

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Data

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Identifying specific TLS-associated genes as potential biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in soft tissue sarcoma.
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10.3389/fimmu.2024.1372692
pmid
38720884
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Xiang-Xu Wang
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Yun-Peng Liu
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Yajie Lu
[3]
Li-Hong Wu
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Jing-Yi Ren
[5]
Hongchen Ji
[6]
Xiaowen Wang
[7]
Hong-Mei Zhang
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Frontiers in immunology
year
2024
abstract
Background: The tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and "MCPcounter" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes. Results: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells. Conclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.
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The prognostic TLS-related genes (P<0.05) were selected by univariate Cox regression analysis based on selected DEGs in the TCGA training cohort. Two prognostic TLS-related hub genes (DUSP9 and TNFSF14) were finally screened for LASSO and multivariate COX regression analysis.
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The prognostic TLS-related genes (P<0.05) were selected by univariate Cox regression analysis based on selected DEGs in the TCGA training cohort. Two prognostic TLS-related hub genes (DUSP9 and TNFSF14) were finally screened for LASSO and multivariate COX regression analysis.
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Using 256 RNA-seq samples from TCGA-SARC and 7 single-cell sequencing samples from GSE212527, the study applied univariate, LASSO, and multivariate Cox analyses to select TLS-related and prognosis-significant hub genes.
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oma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were co
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rcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8,
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tissue sarcoma patients under immunotherapy. Flow cytometry analysis of immune cell distribution in soft
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The prognostic TLS-related genes (P<0.05) were selected by univariate Cox regression analysis based on selected DEGs in the TCGA training cohort. Two prognostic TLS-related hub genes (DUSP9 and TNFSF14) were finally screened for LASSO and multivariate COX regression analysis.
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However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear.\nMethods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and \"MCPcounter\" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes.\nResults: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells.\nConclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.", "claims": [{"id": "claim-method", "statement": "The prognostic TLS-related genes (P<0.05) were selected by univariate Cox regression analysis based on selected DEGs in the TCGA training cohort. 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