CHINESE JOURNAL OF MEDICINAL GUIDE >
Research Progress on the Mechanism and Treatment of Colorectal Polyps Complicated with Inflammatory Bowel Disease
Received date: 2025-09-29
Revised date: 2025-12-16
Accepted date: 2026-03-18
Online published: 2026-04-21
Patients with inflammatory bowel disease (IBD) have a significantly increased risk of developing colorectal polyps, which represent a critical precancerous lesion for IBD‑associated colorectal cancer. Elucidating the underlying mechanisms and optimizing preventive and therapeutic strategies therefore hold substantial clinical value. Chronic intestinal inflammation drives aberrant activation of key signaling pathways, including Wnt/β‑catenin and STAT3, which serves as the core mechanism of polyp formation and directly leads to dysregulated proliferation and differentiation of intestinal epithelial cells. In addition, epigenetic abnormalities caused by imbalanced DNA methylation patterns and mutations in genes such as TP53, together with disturbances in the gut microbiota accompanied by metabolic alterations in bile acids and short‑chain fatty acids, interact with inflammatory responses to form a vicious cycle that further promotes the development and progression of colorectal polyps. Current clinical management centers on standardized endoscopic surveillance and minimally invasive interventions, supplemented by pharmacologic agents such as 5‑aminosalicylic acid, along with lifestyle modifications and microecological modulation. Potential diagnostic biomarkers including SATB2 and ATF6 have also been identified. However, existing research still faces challenges such as fragmented mechanistic insights, insufficient multicenter validation of biomarkers, and a lack of specific preventive and therapeutic agents. Future efforts should focus on deciphering key molecular targets using multi‑omics technologies and establishing individualized precision prevention and treatment strategies.
DUAN Meng, WANG Pei, DONG Yujing, ZHOU Peng, CHEN Weijie, FAN Zhimin
.
Research Progress on the Mechanism and Treatment
of Colorectal Polyps Complicated with Inflammatory Bowel Disease
[1] Guerrero VD, Lennon R, Avvaru HK, et al. Measuring the concordance between endoscopic and histologic inflammation and its effect on IBD-associated dysplasia[J].Endosc Int Open, 2024, 12(1):E145-E154.
[2] Axelrad JE, Olén O, Söderling J, et al. Inflammatory bowel disease and risk of colorectal polyps: a nationwide population-based cohort study from sweden[J].J Crohns Colitis, 2023, 17(9): 1395-1409.
[3] Abu-freha N, Cohen B, Gordon M, et al. Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population[J].Front Med, 2023, 10: 1225616.
[4] Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system[J].Histopathology, 2020, 76(2): 182-188.
[5] Ahadi M, Sokolova A, Brown I, et al. The 2019 world health organization classification of appendiceal, colorectal and anal canal tumours: An update and critical assessment[J].Pathology (Phila.), 2021, 53(4): 454-461.
[6] Nishio M, Kunisaki R, Shibata W, et al. Serrated polyps in patients with ulcerative colitis: Unique clinicopathological and biological characteristics[J].PloS One, 2023, 18(2): e0282204.
[7] Parian AM, Limketkai BN, Chowdhury R, et al. Serrated epithelial change is associated with high rates of neoplasia in ulcerative colitis patients: A case-controlled study and systematic review with meta-analysis[J].Inflamm Bowel Dis, 2021, 27(9): 1475-1481.
[8] Dejong ME, Nagtegaal ID, VOS S, et al. Increased colorectal neoplasia risk in patients with inflammatory bowel disease and serrated polyps with dysplasia[J].Dig Dis Sci, 2022, 67(12): 5647-5656.
[9] Singhi AD, Waters KM, Makhoul EP, et al. Targeted next-generation sequencing supports serrated epithelial change as an early precursor to inflammatory bowel disease-associated colorectal neoplasia[J].Hum Pathol, 2021, 112: 9-19.
[10] Vanschaik FDM, Mooiweer E, Vander HM, et al. Adenomas in patients with inflammatory bowel disease are associated with an increased risk of advanced neoplasia[J].Inflamm Bowel Dis, 2013, 19(2): 342-349.
[11] Li J, Ji Y, Chen N, et al. Colitis-associated carcinogenesis: Crosstalk between tumors, immune cells and gut microbiota[J].Cell Biosci, 2023, 13: 194.
[12] Gu Y, Zhao H, Zheng L, et al. Non‐coding RNAs and colitis‐associated cancer: mechanisms and clinical applications[J].Clin Transl Med, 2023, 13(5): e1253.
[13] Lee-six H, Olafsson S, Ellis P, et al. The landscape of somatic mutation in normal colorectal epithelial cells[J].Nature, 2019, 574(7779): 532-537.
[14] D’antonio DL, Fantini F, Moscatello C, et al. The interplay among wnt/β- catenin family members in colorectal adenomas and surrounding tissues[J].Biomedicines, 2024, 12(8): 1730.
[15] Saez A, Herrero-fernandez B, Gomez-bris R, et al. Pathophysiology of inflammatory bowel disease: Innate immune system[J].Int J Mol Sci, 2023, 24(2): 1526.
[16] 李艳萍.溃疡性结肠炎癌变机制的研究及结直肠息肉危险因素分析[D].北京:北京协和医学院,2015.
[17] Hankey W, Frankel WL, Groden J. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: Implications for therapeutic targeting[J].Cancer Metastasis Rev, 2018, 37(1): 159-172.
[18] Hisamatsu T, Miyoshi J, Oguri N, et al. Inflammation-associated carcinogenesis in inflammatory bowel disease: clinical features and molecular mechanisms[J].Cells, 2025, 14(8): 567.
[19] Aebisher D, Bartusik-aebisher D, Przygórzewska A, et al. Key interleukins in inflammatory bowel disease—a review of recent studies[J].Int J Mol Sci, 2024, 26(1): 121.
[20] Zhang Z, Huang H, Peng L, et al. SIX4 activation in inflammatory response drives the transformation of colorectal epithelium into inflammation and tumor via feedback-enhancing inflammatory signaling to induce tumor stemness signaling[J].Int J Biol Sci, 2024, 20(12): 4618-4634.
[21] Jiang P, Zheng C, Xiang Y, et al. The involvement of TH17 cells in the pathogenesis of IBD[J].Cytokine Growth Factor Rev, 2023, 69: 28-42.
[22] Chen L, Ruan G, Cheng Y, et al. The role of Th17 cells in inflammatory bowel disease and the research progress[J].Front Immunol, 2022, 13: 1055914.
[23] Lee SH, Kwon J, Cho ML. Immunological pathogenesis of inflammatory bowel disease[J].Intest Res, 2018, 16(1): 26-42.
[24] Yang JY, Jie Z, Mathews A, et al. Intestinal epithelial TBK1 prevents differentiation of T-helper 17 cells and tumorigenesis in mice[J].Gastroenterology, 2020, 159(5): 1793-1806.
[25] Destefanoshields CE, White JR, Chung L, et al. Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy[J].Cancer Discov, 2021, 11(7): 1792-1807.
[26] Jin BR, Chung KS, Hwang S, et al. Rosmarinic acid represses colitis-associated colon cancer: a pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis[J].Neoplasia, 2021, 23(6): 561-573.
[27] Yan S, Chang J, Hao X, et al. Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora[J].Phytomedicine Int J Phytother. Phytopharm, 2022, 102: 154217.
[28] Gui X, Iacucci M, Ghosh S. Dysregulation of IL6/IL6R-STAT3-SOCS3 signaling pathway in IBD-associated colorectal dysplastic lesions as compared to sporadic colorectal adenomas in non-IBD patients[J].Pathol Res. Pract, 2020, 216(11): 153211.
[29] Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth[J].Nature, 2012, 491(7423): 254-258.
[30] SonG Q, Gao Y, Liu K, et al. Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice[J].J Transl Med, 2024, 22: 1028.
[31] Dziaman T, Gackowski D, Guz J, et al. Characteristic profiles of DNA epigenetic modifications in colon cancer and its predisposing conditions-benign adenomas and inflammatory bowel disease[J].Clin Epigenetics, 2018, 10: 72.
[32] Guo X, Li J, Xu J, et al. Gut microbiota and epigenetic inheritance: Implications for the development of IBD[J].Gut Microbes, 2025, 17(1): 2490207.
[33] Johnson DH, Taylor WR, Aboelsoud MM, et al. DNA methylation and mutation of small colonic neoplasms in ulcerative colitis and crohn’s colitis: implications for surveillance[J].Inflamm. Bowel Dis, 2016, 22(7): 1559-1567.
[34] Rosa I, Silva P, Da MS, et al. Methylation patterns in dysplasia in inflammatory bowel disease patients[J].Scand J Gastroenterol., 2020, 55(6): 646-655.
[35] Wanders LK, Cordes M, Voorham Q, et al. IBD-associated dysplastic lesions show more chromosomal instability than sporadic adenomas[J].Inflamm Bowel Dis, 2020, 26(2): 167-180.
[36] Lee H, Rabinovitch PS, Mattis AN, et al. Non‐conventional dysplasia in inflammatory bowel disease is more frequently associated with advanced neoplasia and aneuploidy than conventional dysplasia[J].Histopathology, 2021, 78(6): 814-830.
[37] Miller GC, Liu C, Bettington ML, et al. Traditional serrated adenoma-like lesions in patients with inflammatory bowel disease[J].Hum Pathol, 2020, 97: 19-28.
[38] Haneishi Y, Furuya Y, Hasegawa M, et al. Inflammatory bowel diseases and gut microbiota[J].Int J Mol Sci, 2023, 24(4): 3817.
[39] 尹莉莉.菌群失调参与远端结直肠息肉复发的机制研究[D]. 南昌大学,2024.
[40] Vacante M, Ciuni R, Basile F, et al. Gut microbiota and colorectal cancer development: a closer look to the adenoma-carcinoma sequence[J].Biomedicines, 2020, 8(11): 489.
[41] Cai J, Sun L, Gonzalez FJ. Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis[J].Cell Host Microbe, 2022, 30(3): 289-300.
[42] Palmieri O, Castellana S, Latiano A, et al. Mucosal microbiota from colorectal cancer, adenoma and normal epithelium reveals the imprint of fusobacterium nucleatum in cancerogenesis[J].Microorganisms, 2023, 11(5): 1147.
[43] Wang S, Dong W, Liu L, et al. Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis[J].Mol Carcinog, 2019, 58(7): 1155-1167.
[44] Wang X, Chen H, Yang M, et al. Influence of gut microbiota and immune markers in different stages of colorectal adenomas[J].Front Microbiol, 2025, 16: 1556056.
[45] Senore C, Lorenzetti R, Bellisario C, et al. Colonoscopy surveillance: Guidelines for polyps and IBD[J].Minerva Gastroenterol Dietol, 2016, 62(2): 207-222.
[46] Daperno M. Endoscopy in IBD: when and how?[J].Diagnostics, 2023, 13(22): 3423.
[47] Gordon M , Nigam GB , Sinopoulou V ,et al.Update from 2010 (standard operating procedure): protocol for the 2024 British Society of Gastroenterology Guidelines on colorectal surveillance in inflammatory bowel disease[J].BMJ Open Gastroenterology, 2024, 11(1):1541.
[48] 国家卫生健康委员会.结直肠癌筛查与早诊早治方案(2024年版)[J].消化肿瘤杂志(电子版),2024,16(4):410-411.
[49] Derks MEW, Te GM, Vanlierop LMA, et al. Management of colorectal neoplasia in IBD patients: Current practice and future perspectives[J].J Crohns Colitis, 2024, 18(10): 1726-1735.
[50] Yang MM, Usiskin K, Ahmad HA, et al. Considerations for colorectal neoplasia detection in inflammatory bowel disease clinical trials[J].Dig Dis Basel Switz, 2024, 42(1): 12-24.
[51] Santacroce G, Zammarchi I, Tan CK, et al. Present and future of endoscopy precision for inflammatory bowel disease[J].Dig Endosc, 2024, 36(3): 292-304.
[52] M’koma AE. Inflammatory bowel disease: Clinical diagnosis and surgical treatment-overview[J].Med Kaunas Lith., 2022, 58(5): 567.
[53] Fasulo E, D’amico F, Zilli A, et al. Advancing colorectal cancer prevention in inflammatory bowel disease (IBD): challenges and innovations in endoscopic surveillance[J].Cancers, 2024, 17(1): 60.
[54] Derks MEW, Te GM, Vanlierop LMA, et al. Management of colorectal neoplasia in IBD patients: Current practice and future perspectives[J].J Crohns Colitis, 2024, 18(10): 1726-1735.
[55] Navaneethan U, Parasa S, Venkatesh PGK, et al. Prevalence and risk factors for colonic perforation during colonoscopy in hospitalized inflammatory bowel disease patients[J].J Crohns Colitis, 2011, 5(3): 189-195.
[56] Ishikawa H, Mutoh M, Sato Y, et al. Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial[J].Lancet Gastroenterol Hepatol, 2021, 6(6): 474-481.
[57] Zhang YS, Wang F, Cui SX, et al. Natural dietary compound naringin prevents azoxymethane/dextran sodium sulfate-induced chronic colorectal inflammation and carcinogenesis in mice[J].Cancer Biol Ther, 2018, 19(8): 735-744.
[58] Yu Z, Yue B, Gao R, et al. Gastrodin attenuates colitis and prevents tumorigenesis in mice by interrupting TLR4/MD2/NF-κB signaling transduction[J].Anticancer Agents Med Chem, 2024, 24(11): 853-866.
[59] Valiveti CK, Kumar B, Singh AD, et al. Stable dietary ora-curcumin formulation protects from experimental colitis and colorectal cancer[J].Cells, 2024, 13(11): 957.
[60] Gubatan J, Kulkarni CV, Talamantes SM, et al. Dietary exposures and interventions in inflammatory bowel disease: current evidence and emerging concepts[J].Nutr, 2023, 15(3): 579.
[61] Kumar A, Chinnathambi S, Kumar M, et al. Food intake and colorectal cancer[J].Nutr Cancer, 2023, 75(9): 1710-1742.
[62] Byrd DA, Gomez M, Hogue S, et al. Circulating bile acids and adenoma recurrence in the context of adherence to a high-fiber, high-fruit and vegetable, and low-fat dietary intervention[J].Clin Transl Gastroenterol, 2022, 13(10): e00533.
[63] Arifuzzaman M, Won TH, Yano H, et al. Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation[J].J Exp Med, 2024, 221(5): e20232148.
[64] Vernia F, Valvano M, Longo S, et al. Vitamin D in inflammatory bowel diseases. Mechanisms of action and therapeutic implications[J].Nutr, 2022, 14(2): 269.
[65] Cho YA, Lee J, Oh JH, et al. Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma[J].Sci Rep, 2018, 8: 12899.
[66] Battistini C, Ballan R, Herkenhoff ME, et al. Vitamin D modulates intestinal microbiota in inflammatory bowel diseases[J].Int J Mol Sci, 2020, 22(1): 362.
[67] Zhu Z, Guan X, Liu N, et al. Association between dietary factors and colorectal serrated polyps: A systematic review and meta-analysis[J].Front Nutr, 2023, 10: 1187539.
[68] Ross AC, Taylor CL, Yaktine AL, et al. editors.Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D[M].Washington (DC): National Academies Press (US),2011.
[69] Piovani D, Danese S, Peyrin-biroulet L, et al. Environmental risk factors for inflammatory bowel diseases: An umbrella review of meta-analyses[J].Gastroenterology, 2019, 157(3): 647-659.e4.
[70] Carroll KL, frugé AD, Heslin MJ, et al. Diet as a risk factor for early-onset colorectal adenoma and carcinoma: a systematic review[J].Front Nutr, 2022, 9: 896330.
[71] Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial[J].Jama, 2007, 297(21): 2351-2359.
[72] Lee JE, Willett WC, Fuchs CS, et al. Folate intake and risk of colorectal cancer and adenoma: modification by time[J].Am J Clin Nutr, 2011, 93(4): 817-825.
[73] Ma C, Henn P, Miller C, et al. Loss of SATB2 expression is a biomarker of inflammatory bowel disease-associated colorectal dysplasia and adenocarcinoma[J].Am J Surg Pathol, 2019, 43(10): 1314-1322.
[74] Hanaoka M, Ishikawa T, Ishiguro M, et al. Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia[J].J Gastroenterol, 2018, 53(5): 631-641.
[75] Kane LE, Flood B, Manils J, et al. Caspase-4 has potential utility as a colorectal tissue biomarker for dysplasia and early-stage cancer[J].Gastro Hep Adv, 2025, 4(2): 100552.
[76] Polydorides, Alexandros D, McBride, et al. Serrated colorectal polyps in inflammatory bowel disease[J].Mod Pathol, 2015, 28(12): 1584-1593.
[77] Brcic I, Dawson H, Gröchenig HP, et al. Serrated lesions in inflammatory bowel disease: genotype-phenotype correlation[J].Int J Surg Pathol, 2021, 29(1): 46-53.
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