Ismaili N. Evolving landscape of biomarkers in colorectal cancer: From interleukin-8 to integrated multi-marker strategies. World J Gastrointest Surg 2026; 18(10): 120555 [DOI: 10.4240/wjgs.120555]
Corresponding Author of This Article
Nabil Ismaili, Chairman, Chief Pharmacist, Professor, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Mohammed Taïeb Naciri Street, Anfa City, Hay Hassan Municipality, Casablanca 82403, Casablanca-Settat, Morocco. nismaili@um6ss.ma
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Oncology
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Ismaili N. Evolving landscape of biomarkers in colorectal cancer: From interleukin-8 to integrated multi-marker strategies. World J Gastrointest Surg 2026; 18(10): 120555 [DOI: 10.4240/wjgs.120555]
World J Gastrointest Surg. Oct 27, 2026; 18(10): 120555 Published online Oct 27, 2026. doi: 10.4240/wjgs.120555
Evolving landscape of biomarkers in colorectal cancer: From interleukin-8 to integrated multi-marker strategies
Nabil Ismaili
Nabil Ismaili, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Casablanca 82403, Casablanca-Settat, Morocco
Author contributions: Ismaili N was responsible for conceptualization, methodology, and software validation, formal analysis and investigation, resources, data curation, writing original draft, review and editing, and visualization.
AI contribution statement: We acknowledge the use of generative AI in drafting this manuscript and assume full responsibility for its content. Our usage was limited to DeepSeek and Grammarly for editing and readability, while explicitly excluding ChatGPT and Notebook LM. AI played no role in data handling, analysis, or scientific rationale.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Nabil Ismaili, Chairman, Chief Pharmacist, Professor, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Mohammed Taïeb Naciri Street, Anfa City, Hay Hassan Municipality, Casablanca 82403, Casablanca-Settat, Morocco. nismaili@um6ss.ma
Received: March 3, 2026 Revised: March 18, 2026 Accepted: August 28, 2026 Published online: October 27, 2026 Processing time: 231 Days and 6.5 Hours
Abstract
Interleukin-8 (IL-8) is a pro-inflammatory protein implicated in blood vessel formation, tumor growth, and cancer spread, making it a candidate biomarker in colorectal cancer (CRC). Recent prospective data confirm that serum IL-8 levels are significantly elevated in patients with CRC compared with healthy controls, with moderate diagnostic accuracy (area under the curve, 0.68) and independent predictive value. However, these findings must be interpreted within the contemporary multi-pillar biomarker framework for CRC, where mismatch repair status, RAS/BRAF mutations, tumor laterality, human epidermal growth factor receptor 2 amplification, neurotrophic tyrosine receptor kinase fusions, phosphoinositide 3-kinase pathway alterations, perioperative carcinoembryonic antigen, and postoperative circulating tumor DNA have emerged as key clinically relevant biomarkers with growing levels of evidence. This opinion review critically examines the potential role of Interleukin-8 (IL-8) within this evolving landscape and provides a comprehensive overview of the current biomarker spectrum in CRC. Although IL-8 is consistently overexpressed in CRC and shows promise in multivariable models, substantial heterogeneity in study design, assay platforms, and patient populations limits the generalizability of existing data. IL-8 may represent an investigational complementary biomarker with potential utility in enhancing diagnostic sensitivity in selected subgroups such as carcinoembryonic antigen-negative tumors; however, no prospective study has yet demonstrated a clear incremental clinical benefit when IL-8 is added to established biomarkers. Future research should focus on analytical standardization, prospective multicenter validation, integration into multi-marker algorithms, and exploration of the therapeutic potential of the IL-8/C-X-C motif chemokine receptor 2 axis.
Core Tip: Serum interleukin-8 (IL-8) levels are significantly elevated in patients with colorectal cancer and demonstrate moderate diagnostic accuracy (area under the curve, 0.68). Given this modest discriminatory performance and the absence of external validation, IL-8 does not currently meet the criteria for clinical implementation as a standalone diagnostic biomarker. Although IL-8 has shown independent associations in multivariate analyses, its clinical role remains investigational. Within the evolving biomarker landscape, where mismatch repair status, perioperative carcinoembryonic antigen, and postoperative circulating tumor DNA currently have stronger supportive evidence, IL-8 should be regarded as an investigational biomarker requiring prospective validation before clinical integration. No study to date has demonstrated that IL-8-guided strategies improve clinical outcomes in patients with colorectal cancer.
