Associations between serum biomarkers and gut microbial imbalance in predicting chemotherapy response in colorectal cancer: A retrospective analysis

doi:10.4251/wjgo.v17.i8.108870

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Aug 15, 2025 (publication date) through Aug 14, 2025

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Gastrointest Oncol. Aug 15, 2025; 17(8): 108870
Published online Aug 15, 2025. doi: 10.4251/wjgo.v17.i8.108870

Associations between serum biomarkers and gut microbial imbalance in predicting chemotherapy response in colorectal cancer: A retrospective analysis

Ming-Zhi Ling, Zhen Wan, Biao Hu, Ming-Jing Zhao, Hao-Sheng Gong, Gang Li

Ming-Zhi Ling, Zhen Wan, Biao Hu, Ming-Jing Zhao, Hao-Sheng Gong, Gang Li, Department of Laboratory Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China

Author contributions: Ling MZ and Li G designed the study; Wan Z and Hu B performed the experiments; Zhao MJ and Gong HS analyzed the data; all authors contributed to editorial changes in the manuscript, read and approved the final manuscript.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital, and the study followed the ethical guidelines of the Declaration of Helsinki.

Informed consent statement: Informed consent was obtained from all study participants.

Conflict-of-interest statement: The authors declare that they have no competing interests.

Data sharing statement: No additional data are available.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Gang Li, PhD, Associate Chief Physician, Department of Laboratory Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. ligang65580@126.com

Received: May 14, 2025
Revised: June 8, 2025
Accepted: July 15, 2025
Published online: August 15, 2025
Processing time: 91 Days and 16 Hours

Abstract

BACKGROUND

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Growing evidence suggests that gut microbial dysbiosis plays a crucial role in tumorigenesis and can influence therapeutic responses.

AIM

To explore the associations between serum S100A12 and soluble CD14 (sCD14) levels and gut microbiota alterations in patients with CRC, and to assess the predictive utility of these biomarkers in forecasting chemotherapy response.

METHODS

A retrospective analysis was conducted on 104 patients diagnosed with advanced CRC (CRC group) and 104 age-matched and sex-matched healthy controls. Serum concentrations of S100A12 and sCD14 were measured using enzyme-linked immunosorbent assay. Fecal samples collected before chemotherapy were subjected to 16S rRNA sequencing to profile gut microbial composition. Pearson correlation analysis was used to evaluate the relationship between biomarker levels and microbial abundance. Receiver operating characteristic (ROC) curves were used to assess the predictive performance of S100A12 and sCD14 for chemotherapy response.

RESULTS

CRC patients exhibited significantly higher serum levels of S100A12 and sCD14 compared to healthy individuals (P < 0.05). Patients with moderate to severe gut dysbiosis showed the highest elevations of these biomarkers (P < 0.05). Elevated levels of S100A12 and sCD14 were positively correlated with Fusobacterium nucleatum and Prevotella abundance, and negatively correlated with Faecalibacterium prausnitzii and Akkermansia muciniphila (P < 0.05). Both biomarkers significantly decreased following chemotherapy (P < 0.05). Non-responders to chemotherapy had higher pre-treatment levels of S100A12 and sCD14 compared to responders (P < 0.05). Combined ROC analysis showed improved diagnostic accuracy compared to either marker alone.

CONCLUSION

Serum S100A12 and sCD14 levels are closely associated with gut microbiota imbalance and chemotherapy response in CRC patients. These markers may serve as promising predictive indicators for treatment efficacy and offer potential value in individualized treatment strategies.

Keywords: Colorectal cancer; S100A12; Soluble CD14; Gut dysbiosis; Fusobacterium nucleatum; Chemotherapy response; Biomarkers; Predictive evaluation

Core Tip: This study highlights the potential of S100A12 and soluble CD14 as non-invasive biomarkers for assessing gut microbial imbalance and predicting chemotherapy responsiveness in colorectal cancer. Their integration into clinical decision-making could support more personalized and effective treatment planning.