Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;12(1):1676-1688.
doi: 10.1080/21655979.2021.1921551.

Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Rong Liao  1 , Qi-Zhi Ma  2 , Cong-Ya Zhou  3 , Jun-Jun Li  1 , Ning-Na Weng  1 , Yang Yang  1 , Qing Zhu  1
Affiliations

Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Rong Liao et al. Bioengineered. 2021 Dec.

Abstract

Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.

Keywords: ADAM8; Colorectal cancer (CRC); TILs; TIMER; cibersort; weighted gene co-expression network analysis (WGCNA).

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Construction of WGCNA analysis
Figure 2.
Figure 2.
The enrichment analysis of hub module
Figure 3.
Figure 3.
Identification of hub genes
Figure 4.
Figure 4.
Correlation between three expressed prognostic genes and immune cell infiltration through TIMER
Figure 5.
Figure 5.
Genetic Alteration of hub genes in CRC
Figure 6.
Figure 6.
Co-expression Genes correlated with hub genes in CRC
Figure 7.
Figure 7.
Function analysis and signaling pathways of hub genes
Figure 8.
Figure 8.
Functional experiments of ADAM8
See this image and copyright information in PMC

References

    1. Wittekind C, Compton CC, Greene FL, et al. TNM residual tumor classification revisited. Cancer. 2002;94(9):2511–2516. - PubMed
    1. Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–1964 - PubMed
    1. Dienstmann R, Mason MJ, Sinicrope FA, et al. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study. Ann Oncol. 2017;28(5):1023–1031. - PMC - PubMed
    1. Meyers BM, Cosby R, Quereshy F, et al. Adjuvant Chemotherapy for Stage II and III Colon Cancer Following Complete Resection: a Cancer Care Ontario Systematic Review. Clin Oncol (R Coll Radiol). 2017;29(7):459–465. - PubMed
    1. Yazdanifar M, Barbarito G, Bertaina A, et al. gammadelta T Cells: the Ideal Tool for Cancer Immunotherapy. Cells. 2020;9(5):1305. - PMC - PubMed

Publication types

LinkOut - more resources