00735730

January 22, 2026, 10:50

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Dear Editor, I am writing in response to your invitation to comment on the prospective study by Güneş et al., entitled “Diagnostic value of interleukin-8 in colon cancer,” published in your esteemed journal. The authors provide valuable data reinforcing the role of interleukin-8 (IL-8) as an independent diagnostic biomarker in colon adenocarcinoma. Their work rightly concludes that IL-8 holds promise, particularly as part of a multi-marker panel. I would like to extend this discussion by contextualizing IL-8 within the current, rapidly evolving biomarker landscape of colorectal cancer (CRC), as recently elaborated in an editorial on this topic. The future of CRC management lies in a dynamic, multi-layered biomarker strategy that integrates three key pillars: 1) Mismatch repair (MMR) status to dictate therapeutic class (chemotherapy vs. immunotherapy); 2) Perioperative carcinoembryonic antigen (CEA) for immediate risk stratification, especially within microsatellite stable (MSS) disease; and 3) Postoperative circulating tumor DNA (ctDNA) as a dynamic tool to guide treatment intensity and de-escalation, as definitively demonstrated by the recent AGITG DYNAMIC-III trial. In this framework, the findings on IL-8 by Güneş et al. present a compelling opportunity. While its standalone diagnostic accuracy (AUC=0.68) is moderate, its independent predictive value suggests a distinct biological role, likely rooted in its pro-inflammatory and angiogenic functions. This positions IL-8 not as a replacement for the aforementioned pillars, but as a potential complementary element, particularly within the MSS cohort. Specifically, IL-8 could enhance the second pillar (risk stratification) by providing additional biological granularity. For instance, in MSS patients with normal or borderline CEA levels, an elevated IL-8 might signal a more aggressive tumor biology driven by inflammation, potentially identifying a subset that would benefit from closer surveillance or adjuvant therapy. Furthermore, given its link to angiogenesis and immune modulation, IL-8 merits investigation as a predictive biomarker for responses to anti-angiogenic therapies (e.g., bevacizumab) and possibly immunotherapy, even in MSS/pMMR tumors. Therefore, I propose that the next logical step for research, as inspired by both this study and the broader editorial perspective, is to evaluate IL-8 within integrated multi-marker panels. Combining IL-8 with CEA, ctDNA, and potentially other inflammatory markers (e.g., CRP) in algorithm-driven models could significantly improve diagnostic sensitivity, prognostic stratification, and predictive accuracy. This approach aligns perfectly with the paradigm of dynamic precision oncology, where multiple data streams are synthesized to guide personalized therapeutic navigation. I congratulate the authors on their contribution and thank you for the opportunity to share these perspectives, hoping they may stimulate further research into the integrative potential of IL-8 within the modern CRC biomarker ecosystem. Sincerely, Pr Nabil Ismaili Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Hrealth (FM6SS), Casablanca, Morocco, nismaili@um6ss.ma, 0000-0001-5786-5134

Replied on January 31, 2026, 11:01

We thank the commentator for the insightful and thoughtful perspectives provided. We fully agree that IL-8 is not a strong diagnostic biomarker when used as a standalone parameter. In line with this view, our study does not propose IL-8 as a replacement for established biomarkers, but rather aims to contribute objective prospective data to clarify where IL-8 may fit within the complex prognostic and risk stratification frameworks of colorectal cancer. We hope that our findings will be useful in informing future integrated, multi-marker approaches and in defining the complementary role of IL-8 in colorectal cancer assessment. We sincerely appreciate the valuable comments and the opportunity to further contextualize our results.