Transcriptome of CD8+ tumor-infiltrating T cells : a link between diabetes and colorectal cancer

Saleh, R, Sasidharan Nair, V, Murshed, K, Abu Nada, M, Elkord, E ORCID: https://orcid.org/0000-0002-3868-0318 and Shaheen, R 2021, 'Transcriptome of CD8+ tumor-infiltrating T cells : a link between diabetes and colorectal cancer' , Cancer Immunology, Immunotherapy, 70 (9) , pp. 2625-2638.

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Abstract

There is an increased risk of colorectal cancer (CRC) development in patients with non-insulin-dependent type 2 diabetes. CD8 T cells have been implicated in diabetes and are crucial for anti-tumor immunity. However, transcriptomic profiling for CD8 T cells from CRC diabetic patients has not been explored. We performed RNA sequencing and compared transcriptomic profiles of CD8  tumor-infiltrating T lymphocytes (CD8 TILs) in CRC diabetic patients with CRC nondiabetic patients. We found that genes associated with ribogenesis, epigenetic regulations, oxidative phosphorylation and cell cycle arrest were upregulated in CD8 TILs from diabetic patients, while genes associated with PI3K signaling pathway, cytokine response and response to lipids were downregulated. Among the significantly deregulated 1009 genes, 342 (186 upregulated and 156 downregulated) genes were selected based on their link to diabetes, and their associations with the presence of specific CRC pathological parameters were assessed using GDC TCGA colon database. The 186 upregulated genes were associated with the presence of colon polyps history (P = 0.0007) and lymphatic invasion (P = 0.0025). Moreover, CRC patients with high expression of the 186 genes were more likely to have poorer disease-specific survival (DSS) (Mantel-Cox log-rank P = 0.024) than those with low score. Our data provide novel insights into molecular pathways and biological functions, which could be altered in CD8 TILs from CRC diabetic versus nondiabetic patients, and reveal candidate genes linked to diabetes, which could predict DSS and pathological parameters associated with CRC progression. However, further investigations using larger patient cohorts and functional studies are required to validate these findings.

Item Type: Article
Additional Information: ** From PubMed via Jisc Publications Router **Journal IDs: eissn 1432-0851 **Article IDs: pubmed: 33582867; pii: 10.1007/s00262-021-02879-7 **History: accepted 01-02-2021; submitted 10-09-2020
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Cancer Immunology, Immunotherapy
Publisher: Springer
ISSN: 0340-7004
Related URLs:
Funders: Qatar Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 04 May 2021 14:20
Last Modified: 27 Aug 2021 21:51
URI: http://usir.salford.ac.uk/id/eprint/59712

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