Effects of Serum S100A12 and Diamine Oxidase Levels on Gut Microbiota Dysbiosis and Immune Function in Patients with Colon Cancer
Abstract
Colon cancer, a leading cause of death, demands early detection. We evaluate serum S100 calcium-binding protein A12 (S100A12) and diamine oxidase (DAO) effects on gut dysbiosis/immunity and their combined diagnostic value.
This retrospective study included 105 colon cancer patients (study group), 90 benign lesions, and 105 matched healthy controls. Serum S100A12 and DAO were measured by ELISA (enzyme-linked immunosorbent assay). Gut flora (Escherichia coli, Enterococcus faecalis, Bifidobacterium, Lactobacillus) were cultured; T cell subsets (CD4+, CD8+, Treg) by flow cytometry. Patients were stratified by median levels into high/low groups. Correlations and diagnostic efficacy were assessed using Pearson test and ROC (receiver operating characteristic) analysis.
Baseline data were comparable among three groups. Fecal flora (E. coli, E. faecalis, Bifidobacterium, Lactobacillus) and T cells (CD4+, CD8+, regulatory T cells) differed significantly. Serum S100A12 and DAO were elevated in colon cancer versus benign/control groups. High/low subgroups showed disparities in flora and T cells. S100A12 and DAO positively correlated with E. coli/E. faecalis, CD8+ T, and Treg, but negatively with Bifidobacterium, Lactobacillus, and CD4+ T. The cancer group had reduced CD4+ and CD4+/CD8+ ratio, and elevated CD8+ and Treg. Combined S100A12+DAO detection outperformed single markers.
Elevated serum S100A12 and DAO in colon cancer are associated with gut microbiota dysbiosis and immune dysregulation. Their combination shows promise as a potential biomarker for early diagnosis and disease evaluation.
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29. Liu Y, Lau HC, Cheng WY, Yu J. Gut microbiome in colorectal cancer: clinical diagnosis and treatment. Genomics Proteomics Bioinformatics. 2023;21(1):84-96.
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33. Shu P, Zhao L, Wagn J, Shen X, Zhang X, Shen S, et al. [Association between serum levels of S100A8/S100A9 and clinical features of colorectal cancer patients]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016.
34. Luo CT, Li MO. Transcriptional control of regulatory T cell development and function. Trends Immunol. 2013;34(11):531-9.
35. Zhong T, Sun S, Zhao M, Zhang B, Xiong H. The mechanisms and clinical significance of CD8(+) T cell exhaustion in anti-tumor immunity. Cancer Biol Med. 2025;22(5):460-80.
36. Testa U, Pelosi E, Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel). 2018;6(2).
37. Snezhkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV, Krasnov GS, et al. ROS generation and antioxidant defense systems in normal and malignant cells. Oxid Med Cell Longev. 2019;2019:6175804.
38. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277.
2. Nambidi S, Shruthi KB, Kanimozhe SP, Banerjee A, Kondaveeti SB, Duttaroy AK, et al. A review of circular RNAs in colorectal cancer: insights into biomarker discovery and therapeutic targeting. Front Oncol. 2025;15.
3. Ionescu VA, Diaconu CC, Gheorghe G, Mihai M-M, Diaconu CC, Bostan M, et al. Gut microbiota and colorectal cancer: a balance between risk and protection. Int J Mol Sci. 2025;26(8):3733.
4. Tudorache M, Treteanu A-R, Gradisteanu Pircalabioru G, Lixandru-Petre I-O, Bolocan A, Andronic O. Gut microbiome alterations in colorectal cancer: mechanisms, therapeutic strategies, and precision oncology perspectives. Cancers. 2025;17(14):2294.
5. Kang Z, Jiang S, Fang J-Y, Chen H. Intestinal dysbiosis and colorectal cancer. Chin Med J. 2025;138(11):1266-87.
6. Palmieri O, Castellana S, Latiano A, Latiano T, Gentile A, Panza A, et al. Mucosal microbiota from colorectal cancer, adenoma and normal epithelium reveals the imprint of Fusobacterium nucleatum in cancerogenesis. Microorganisms. 2023;11(5):1147.
7. Rezaee MA, Nouri R, Hasani A, Asgharzadeh M, Sefidan FY, Hemmati F. Roles of gut microbiota in colorectal carcinogenesis providing a perspective for early diagnosis and treatment. Curr Pharm Biotechnol. 2022;23(13):1569-80.
8. Liang JQ, Zeng Y, Lau EYT, Sun Y, Huang Y, Zhou T, et al. A probiotic formula for modulation of colorectal cancer risk via reducing CRC-associated bacteria. Cells. 2023;12(9):1244.
9. Nigam M, Mishra AP, Deb VK, Dimri DB, Tiwari V, Bungau SG, et al. Evaluation of the association of chronic inflammation and cancer: insights and implications. Biomed Pharmacother. 2023;164:115015.
10. Jalalvand M, Enayati S, Akhtari M, Madreseh E, Jamshidi A, Farhadi E, et al. Blood regulatory T cells in inflammatory bowel disease, a systematic review, and meta-analysis. Int Immunopharmacol. 2023;117:109824.
11. Hanahan D, Michielin O, Pittet MJ. Convergent inducers and effectors of T cell paralysis in the tumour microenvironment. Nat Rev Cancer. 2024;25(1):41-58.
12. Chen X, Ma Z, Yi Z, Wu E, Shang Z, Tuo B, et al. The effects of metabolism on the immune microenvironment in colorectal cancer. Cell Death Discov. 2024;10(1).
13. Xie L, Fang J, Yu J, Zhang W, He Z, Ye L, et al. The role of CD4+ T cells in tumor and chronic viral immune responses. MedComm. 2023;4(5).
14. Guo X, Xu L, Nie L, Zhang C, Liu Y, Zhao R, et al. B cells in head and neck squamous cell carcinoma: current opinion and novel therapy. Cancer Cell Int. 2024;24(1).
15. Wang X, Luo Y, Zhou Q, Ma J. The roles of S100A8/A9 and S100A12 in autoimmune diseases: mechanisms, biomarkers, and therapeutic potential. Autoimmun Rev. 2025;24(12):103920.
16. Chen J, Huang Y, Wang B, Lu Y, Jian J, Tang J, et al. Characterization of S100A12 from nile tilapia (Oreochromis niloticus) and its roles on inflammatory responses. Fish Shellfish Immunol. 2022;131:401-7.
17. Hou FEI, Wang L, Wang H, Gu J, Li M, Zhang J, et al. Elevated gene expression of S100A12 is correlated with the predominant clinical inflammatory factors in patients with bacterial pneumonia. Mol Med Rep. 2015;11(6):4345-52.
18. Yang X, Zhang W, Wang L, Zhao Y, Wei W. Metabolite-sensing GPCRs in rheumatoid arthritis. Trends Pharmacol Sci. 2024;45(2):118-133.
19. Chien Y-C, Chen J-N, Chen Y-H, Chou R-H, Lee H-C, Yu Y-L. Epigenetic silencing of miR-9 promotes migration and invasion by EZH2 in glioblastoma cells. Cancers. 2020;12(7):1781.
20. Wang J, He M, Yang M, Ai X. Gut microbiota as a key regulator of intestinal mucosal immunity. Life Sci. 2024;345:122612.
21. Shi L, Li Y, Liu Y, Jia H. Alterations of gut microbiota and cytokines in elevated serum diamine oxidase disorder. Medicine. 2022;101(50).
22. Nong K, Qin X, Liu Z, Wang Z, Wu Y, Zhang B, et al. Potential effects and mechanism of flavonoids extract of Callicarpa nudiflora Hook on DSS-induced colitis in mice. Phytomedicine. 2024;128:155523.
23. Efremova I, Maslennikov R, Medvedev O, Kudryavtseva A, Avdeeva A, Krasnov G, et al. Gut microbiota and biomarkers of intestinal barrier damage in cirrhosis. Microorganisms. 2024;12(3):463.
24. Yu Y, Zhao W, Yang M, Wu B, Yuan X. Tumor-promoting gut microbes in colorectal cancer: mechanisms and translational perspectives. Int J Med Sci. 2026;23(1):63-75.
25. Chaturvedi P, Pathak R, Dayal R, Parihar H, Kathireshan AK, Tirumalai PS. Colorectal cancer mitigation through probiotics: current evidence and future directions. Curr Microbiol. 2025;82(8):339.
26. Hospital Authority of National Health Commission of the People's Republic of China; Chinese Society of Oncology CMA. Chinese protocol of diagnosis and treatment of colorectal cancer of the National Health Commission (2023 edition). Chin J Pract Surg. 2023;43(6):1005-2208.
27. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6(1):e16393.
28. Gianotti L, Braga M, Fortis C, Soldini L, Vignali A, Colombo S, et al. A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. JPEN J Parenter Enteral Nutr. 1999;23(6):314-20.
29. Liu Y, Lau HC, Cheng WY, Yu J. Gut microbiome in colorectal cancer: clinical diagnosis and treatment. Genomics Proteomics Bioinformatics. 2023;21(1):84-96.
30. Maecker HT, Rinfret A, D'Souza P, Darden J, Roig E, Landry C, et al. Standardization of cytokine flow cytometry assays. BMC Immunol. 2005;6:13.
31. Li Y, Yang J, Wu Q. Correlation between serum S100A12 and sRAGE levels with intestinal flora imbalance and chemotherapy effect in patients with colon cancer. Anhui Med Pharm J. 2024;28(6):1170-3.
32. Qiao SB, Niu ML, Liang WT, Zhang LJ, Chen X, Zhu YK. Analysis of serum S100A12, soluble advanced glycation end products receptor, and gut microbiome in elderly patients with colorectal cancer. World J Gastrointest Oncol. 2025;17(6):106393.
33. Shu P, Zhao L, Wagn J, Shen X, Zhang X, Shen S, et al. [Association between serum levels of S100A8/S100A9 and clinical features of colorectal cancer patients]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016.
34. Luo CT, Li MO. Transcriptional control of regulatory T cell development and function. Trends Immunol. 2013;34(11):531-9.
35. Zhong T, Sun S, Zhao M, Zhang B, Xiong H. The mechanisms and clinical significance of CD8(+) T cell exhaustion in anti-tumor immunity. Cancer Biol Med. 2025;22(5):460-80.
36. Testa U, Pelosi E, Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel). 2018;6(2).
37. Snezhkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV, Krasnov GS, et al. ROS generation and antioxidant defense systems in normal and malignant cells. Oxid Med Cell Longev. 2019;2019:6175804.
38. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277.
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| Amine oxidase (Copper-Containing) Colonic neoplasms Gastrointestinal microbiome Immunity; S100A12 protein | ||
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How to Cite
1.
Liu J, Liu S, Cong J, Zhao X, Zhang L, Li W. Effects of Serum S100A12 and Diamine Oxidase Levels on Gut Microbiota Dysbiosis and Immune Function in Patients with Colon Cancer. Iran J Allergy Asthma Immunol. 2026;:1-15.
