IL6 and IL6R as prognostic biomarkers in colorectal cancer (original) (raw)

Pennel, K. et al. (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer.Biomolecules, 14(12), 1629. (doi: 10.3390/biom14121629)

Abstract

Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome. However, evidence is more limited for the role of IL6 and its cognate receptor, IL6R, within the tumour epithelium and microenvironment. This study aimed to investigate IL6 and IL6R expression in a large cohort of retrospectively collected patient tumour specimens and determine association with clinical outcomes and characteristics. High expression of IL6R in the tumour epithelium was associated with reduced cancer-specific survival in patients with right-sided colon cancer. In these patients, high IL6R expression was also associated with an increased systemic neutrophil-to-lymphocyte ratio. A high number of copies of IL6 mRNA within the tumour-associated stroma, but not epithelium, was associated with reduced cancer-specific survival. The results from this study have validated IL6R as a marker of poor prognosis in a subgroup of CRC patients and identified the spatially resolved prognostic nature of intra-tumoural IL6 expression. This study has also highlighted the need for investigation of IL6/IL6R-targeted therapies as novel treatment strategies for patients with colon cancer.

Item Type: Articles
Additional Information: The authors would like to acknowledge funding from Chief Scientific Office (EPD/22/13)(TCS/22/02) and CRUK (CTRQQR-2021\100006). Beatson Cancer Charity (24-25-045 BCC).
Keywords: Colorectal cancer, interleukin-6, interleukin-6 receptor, prognosis, biomarker, sidedness, inflammation .
Status: Published
Refereed: Yes
Glasgow Author(s) Enlighten ID: Nixon, Mr Colin and Al-Badran, Ms Sara and Pennel, Dr Kathryn and Roxburgh, Professor Campbell and Quinn, Dr Jean and Edwards, Professor Joanne and Schubert Santana, Ms Leonor Patricia and McMillan, Professor Donald and Hatthakarnkul, Miss Phimmada
Creator Roles: Pennel, K.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review and editingAl-Badran, S. S. F.Investigation, Formal analysis, Validation, Writing – review and editingSchubert Santana, L.Investigation, Formal analysisQuinn, J.Supervision, MethodologyNixon, C.Methodology, ResourcesRoxburgh, C.Conceptualization, Supervision, Funding acquisition, Resources, Writing – review and editingMcMillan, D.Conceptualization, Supervision, Funding acquisition, Resources, Writing – review and editingEdwards, J.Conceptualization, Supervision, Investigation, Funding acquisition, Project administration, Resources, Writing – review and editing
Authors: Pennel, K., Kurniawan, A., Al-Badran, S. S. F., Schubert Santana, L., Quinn, J., Nixon, C., Hatthakarnkul, P., Maka, N., Roxburgh, C., McMillan, D., and Edwards, J.
College/School: College of Medical Veterinary and Life Sciences > School of Cancer SciencesCollege of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name: Biomolecules
Publisher: MDPI
ISSN: 2218-273X
ISSN (Online): 2218-273X
Published Online: 19 December 2024
Copyright Holders: Copyright © 2024 The Authors
First Published: First published in Biomolecules 14(12)1629
Publisher Policy: Reproduced under a Creative Commons licence

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Funder and Project Information

An investigation into the therapeutic potential of combining radiotherapy and IKK inhibition for rectal cancer patients

Kathryn Pennel

EPD/22/13

School of Cancer Sciences

IL6/JAK/STAT3 pathway in colorectal cancer

Joanne Edwards

TCS/22/02

SCS - Translational Pharmacology Lab

CRUK Centre Renewal 2021

Owen Sansom

CTRQQR-2021\100006

SCS - Beatson Institute for Cancer Research

New Digital Slide Scanner at Glasgow Tissue Research Facility

Joanne Edwards

24-25-045

SCS - Therapeutic Science Research

Deposit and Record Details

ID Code: 343675
Depositing User: Mr Alastair Arthur
Datestamp: 17 Dec 2024 08:47
Last Modified: 23 Dec 2024 13:30
Date of acceptance: 17 December 2024
Date of first online publication: 19 December 2024
Date Deposited: 17 December 2024
Data Availability Statement: Yes