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Differential gene expression of tumor-infiltrating CD4+ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

journal contribution
submitted on 2024-07-02, 09:33 and posted on 2024-07-02, 12:13 authored by Varun Sasidharan Nair, Reem Saleh, Rowaida Z Taha, Salman M Toor, Khaled Murshed, Ayman A Ahmed, Mohamed A Kurer, Mohamed Abu Nada, Fares Al Ejeh, Eyad Elkord

Tumor-infiltrating lymphocytes (TILs) play indispensable roles in the progression and response to treatment of solid tumors. However, the prognostic significance of CD4+ TILs is not fully disclosed in cancers generally and in CRC in particular, mainly due to the existence of different functional subsets of CD4+ T cells. We performed transcriptomic profiling of CD4+ TILs isolated from CRC patients in order to identify differentially expressed genes and their functional pathways in early versus advanced disease stages. We found that in advanced stages, genes related to immune and inflammatory responses, in particular Th1-mediated immune response and cytotoxicity-mediated genes, were downregulated; while epigenetic-mediated silencing genes were upregulated. Interestingly, we identified genes, which were steadily upregulated or downregulated in CD4+ TILs with CRC progression from stage I to IV. Additionally, of the top 200 deregulated genes, 43 upregulated and 64 downregulated genes showed similar deregulation trends in the cancer genome atlas CRC dataset. From these 97 deregulated genes, we identified a “poor prognosis CD4 gene signature (ppCD4sig)”. Patients with high ppCD4sig score showed shorter disease-specific survival (DSS) and progression-free interval (PFI). The ppCD4sig was an independent prognostic indicator for DSS (HR = 1.73, 95% CI 1.32–2.27, P = 0.0001) and PFI (HR = 1.75, 95% CI 1.3–2.35, P = 0.0016). Additionally, patients at advanced stages and at a younger age (<55 years) were more likely to have a high ppCD4sig score. Altogether, our data provide novel insights and a unique prognostic gene signature of CD4+ TILs in the CRC microenvironment.

Other Information

Published in: OncoImmunology
License: http://creativecommons.org/licenses/by-nc/4.0/
See article on publisher's website: https://dx.doi.org/10.1080/2162402x.2020.1825178

Funding

Open Access funding provided by the Qatar National Library.

Hamad Bin Khalifa University, Qatar Biomedical Research Institute (VR04).

History

Language

  • English

Publisher

Taylor & Francis

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC