基于生物信息学分析的内皮细胞衍生转录组在结肠癌中的作用。

Contribution of endothelial cell-derived transcriptomes to the colon cancer based on bioinformatics analysis.

机构信息

Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.

School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

出版信息

Math Biosci Eng. 2021 Aug 27;18(6):7280-7300. doi: 10.3934/mbe.2021360.

DOI:10.3934/mbe.2021360

PMID:34814249

Abstract

UNLABELLED

Colon tumor endothelial cells (CTECs) plays substantial roles to induce immune invasion, angiogenesis and metastasis. Thus, identification of the CTECs-derived transcriptomes could be helpful for colon cancer diagnosis and potential therapy.

METHODS

By analysis of CTECs-derived gene expression profiling dataset, we identified differentially expressed genes (DEGs) between CTECs and colon normal endothelial cells (CNECs). In addition, we identified the significant pathways and protein-protein interaction (PPI) network that was significantly associated with the DEGs. Furthermore, we identified hub genes whose expression was significantly associated with prognosis and immune cell infiltrations in colon cancer. Finally, we identified the significant correlations between the prognostic hub genes and immune-inhibitory markers in colon cancer.

RESULTS

We identified 362 DEGs in CTECs relative to the CNECs, including117 up-regulated genes and 245 down-regulated genes in the CTECs. In addition, we identified significantly up-regulated pathways in CTECs that were mainly involved in cancer and immune regulation. Furthermore, we identified hub genes (such as SPARC, COL1A1, COL1A2 and IGFBP3) that are associated with prognosis and immune cells infiltrations in colon cancer. Interestingly, we found that prognosis-associated hub genes (SPARC, COL1A1, COL1A2 and IGFBP3) are positively correlated with immune-inhibitory markers of various immunosuppressive cells, including TAM, M2 macrophage, Tregs and T cell exhaustion. Finally, our findings revealed that prognosis-associated upregulated hub genes are positively correlated with immune checkpoint markers, including PD-L1 and PD-L2 and the immunosuppressive markers including TGFB1 and TGFBR1.

CONCLUSIONS

The identification of CTECs-specific transcriptomes may provide crucial insights into the colon tumor microenvironment that mediates the development of colon cancer.

摘要

未加标签

结肠肿瘤内皮细胞（CTECs）在诱导免疫浸润、血管生成和转移方面起着重要作用。因此，鉴定 CTECs 衍生的转录组可能有助于结肠癌的诊断和潜在治疗。

方法

通过分析 CTECs 衍生的基因表达谱数据集，我们鉴定了 CTECs 与结肠正常内皮细胞（CNECs）之间差异表达的基因（DEGs）。此外，我们还鉴定了与 DEGs 显著相关的显著途径和蛋白质-蛋白质相互作用（PPI）网络。此外，我们鉴定了表达与结肠癌预后和免疫细胞浸润显著相关的关键基因。最后，我们鉴定了预后关键基因与结肠癌免疫抑制标志物之间的显著相关性。

结果

我们在 CTECs 中鉴定了 362 个 DEGs，其中 CTECs 中上调基因 117 个，下调基因 245 个。此外，我们鉴定了 CTECs 中显著上调的途径，这些途径主要涉及癌症和免疫调节。此外，我们鉴定了与结肠癌预后和免疫细胞浸润相关的关键基因（如 SPARC、COL1A1、COL1A2 和 IGFBP3）。有趣的是，我们发现与预后相关的关键基因（SPARC、COL1A1、COL1A2 和 IGFBP3）与各种免疫抑制细胞的免疫抑制标志物呈正相关，包括 TAM、M2 巨噬细胞、Tregs 和 T 细胞耗竭。最后，我们的研究结果表明，与预后相关的上调关键基因与免疫检查点标志物（包括 PD-L1 和 PD-L2）以及免疫抑制标志物（包括 TGFB1 和 TGFBR1）呈正相关。