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

Jie Wang; Md Nazim Uddin; Rehana Akter; Yun Wu

doi:10.3934/mbe.2021360

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

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

Authors

Jie Wang^{1

2}, Md Nazim Uddin^{2

3}, Rehana Akter⁴, Yun Wu⁵

Affiliations

¹ Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
² School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
³ Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka 1205, Bangladesh.
⁴ Bioinformatics Research Lab, Center for Research Innovation and Development (CRID), Dhaka, Bangladesh.
⁵ Department of General Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.

PMID: 34814249
DOI: 10.3934/mbe.2021360

Abstract

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.

Keywords: colon tumor endothelial cells; colon tumor microenvironment; immune-inhibitory markers; immunosuppressive cells; prognostic hub genes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colonic Neoplasms* / genetics
Computational Biology*
Endothelial Cells
Gene Expression Regulation, Neoplastic
Humans
Protein Interaction Maps
Transcriptome
Tumor Microenvironment / genetics