Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.
Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.
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靶向淋巴毒素 Beta 和配对框 5：软组织肉瘤转移的潜在治疗策略。
DOI：
10.1186/s12935-020-01632-x
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发表时间：
2021-01-04
影响因子：
5.8
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Huang R;Zeng Z;Yan P;Yin H;Zhu X;Hu P;Zhuang J;Li J;Li S;Song D;Meng T;Huang Z
软组织肉瘤（STS）具有较高的早期转移率。在本研究中，我们旨在揭示具有差异表达基因和肿瘤浸润细胞的STS的潜在转移机制和相关信号通路。从癌症基因组图谱（Cancer Genome Atlas， TCGA）数据库下载261例STS样本，采用RNA-seq测序方法鉴定与转移相关的差异表达免疫基因和转录因子（transcription factors, TFs），通过Pearson相关分析构建两者之间的关系。基于最显著免疫基因建立转移相关预测模型。采用CIBERSORT算法鉴定与关键免疫基因共表达的显著免疫细胞。通过GSVA和GSEA来确定与预后相关的KEGG通路。最后，我们使用Pearson相关分析来探索免疫基因、免疫细胞和KEGG通路之间的关系。此外，通过单细胞RNA测序和ChIP测序数据验证了关键基因及其调控机制。共鉴定出204个免疫基因和12个tf。该预测模型对远处转移的预测效果满意，曲线下面积（AUC）为0.808。LTB与PAX5 （P < 0.001, R = 0.829）和造血细胞谱系通路（P < 0.001, R = 0.375）显著相关。通过ChIP测序数据验证了PAX5和LTB之间的转录调控模式。我们假设STSs中PAX5 （TF）调控的LTB（免疫基因）下调可能具有诱导STSs患者癌细胞转移的能力。
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.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.3390/molecules23061479
发表时间：
2018-06-19
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lambert M;Jambon S;Depauw S;David-Cordonnier MH
通讯作者：
David-Cordonnier MH
影响因子：
12.3
作者：
Chen W;Li Y;Easton J;Finkelstein D;Wu G;Chen X
通讯作者：
Chen X
DOI：
10.1016/s0959-8049(09)70033-4
发表时间：
2009-09-01
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
--
作者：
Johnsen, Hans Erik;Kjeldsen, Malene Krag;Dybkaer, Karen
通讯作者：
Dybkaer, Karen
影响因子：
64.5
作者：
BROWNING, JL;NGAMEK, A;WARE, CF
通讯作者：
WARE, CF