Zhao XJ, Qiu XY. Adjacent nontumor mucosa: The overlooked frontier in colorectal cancer prognostication. World J Gastroenterol 2026; 32(20): 119322 [DOI: 10.3748/wjg.v32.i20.119322]
Corresponding Author of This Article
Xin-Yun Qiu, MD, PhD, Adjunct Associate Professor, Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, United States. qiuxinyun2819@126.com
Research Domain of This Article
Immunology
Article-Type of This Article
Opinion Review
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World J Gastroenterol. May 28, 2026; 32(20): 119322 Published online May 28, 2026. doi: 10.3748/wjg.v32.i20.119322
Adjacent nontumor mucosa: The overlooked frontier in colorectal cancer prognostication
Xiao-Jing Zhao, Xin-Yun Qiu
Xiao-Jing Zhao, Xin-Yun Qiu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Xin-Yun Qiu, Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: Qiu XY and Zhao XJ conceived the study; Qiu XY wrote the manuscript. Both authors approved the final manuscript.
AI contribution statement: ChatGPT was only used for language polishing purposes. All scientific content, including the Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion, was written by the authors. ChatGPT was used solely for language polishing and improving readability. It was not used to generate or develop the scientific content. The study design, data interpretation, and all conclusions were developed by the authors without AI involvement. The figure was prepared by the authors using standard software (e.g., PowerPoint).
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Corresponding author: Xin-Yun Qiu, MD, PhD, Adjunct Associate Professor, Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, United States. qiuxinyun2819@126.com
Received: January 26, 2026 Revised: March 1, 2026 Accepted: March 13, 2026 Published online: May 28, 2026 Processing time: 116 Days and 8.8 Hours
Abstract
Immune contexture increasingly shapes colorectal cancer (CRC) prognosis, yet most profiling is tumor-centric. The study interrogated adjacent nontumor mucosa (NM) and tumor center (TC) in 99 CRC patients with liver metastases (LM). Using immunohistochemistry for CD68 (M0), CD80 (M1), and CD206/CD163 (M2), they observed a consistent density gradient (CD163 > CD206 > CD68 > CD80) and markedly lower macrophage densities in TC vs NM, consistent with immune exclusion. Crucially, stage-specific prognostic signals resided in NM: Higher CD80+ density associated with longer overall survival (OS) in stage I-III, while higher CD163+ density associated with longer OS in stage IV; these persisted in multivariable models. NM likely captures “immunological field cancerization,” reflecting systemic immune tone, pre-metastatic niche cues, and therapy-induced reprogramming masked within the tumor core. Clinically, incorporating NM macrophage markers (CD80, CD163) into routine pathology, combined with T-cell based metrics, could refine risk stratification and guide stage-tailored immune modulation. Strengths include paired NM-TC analysis and whole-slide quantification; retrospective design and phenotypic readouts are limitations. Prospective validation and spatial/functional omics are warranted. Overall, this study positions NM as an overlooked but actionable immune compartment, with potential to improve decision-making and outcomes for CRC patients with LM.
Core Tip: Most immune profiling in colorectal cancer focuses on the tumor core, overlooking adjacent nontumor mucosa (NM). The study show that NM macrophage subsets provide stage-specific prognostic signals after liver metastasectomy: Higher CD80-positive (M1-like) macrophages predict longer survival in stage I-III, while higher CD163-positive (M2-like) macrophages predict longer survival in stage IV. Tumor center metrics were not predictive. Incorporating NM immune profiling (CD80, CD163), alongside T-cell measures, could refine risk stratification and guide stage-tailored immune modulation.
