Correlation of NF-kappa B and beta catenin expression for enhancing monitoring accuracy and complications risk in patients with IBD

Aims Inflammatory bowel disease (IBD) is a chronic pathology, whose most important complication is colitis associated cancer (CAC). The link between inflammation and cancer has been excessively investigated. In this context, the correlation between NF-kappa B and beta-catenin has been studied by numerous authors, but the results were contradictory. Our study will contribute in clarifying this issue, moreover by performing IHC analysis in human colorectal tissues [1] [2] [3] [4] [5] [6] [7] [8] [9].

Methods In this cross-sectional study, tissue samples were collected from patients who underwent colonoscopy for confirmation/evaluation of IBD, including its both forms: Crohn’s disease and ulcerative colitis. Immunohistochemostry (IHC) using monoclonal antibodies was performed for NF kappa B and beta catenin. Staining patterns were evaluated, by including analysis of both expression and localization.

Results NF kappaB and beta catenin were upregulated in colorectal tissues of patients suffering from IBD, compared with controls. We found a significant positive correlation (p=0.037) of immunohistochemical expression of these markers, both involved in malignant alteration of inflamed colon cells. Nuclear beta catenin expression was found in 11.1% of patients with IBD, while nuclear NF kappa B expression was 47.2%. Interestingly, overexpresson of beta catenin was more remarkable in colon cells of patients with Crohn’s disease.

Conclusions Our findings indicate that NF kappa B and beta catenin could serve as diagnostic and prognostic markers in the development of CAC in patients with IBD. This study contributes in establishing most useful molecular markers, which can predict the risk for mucosal dysplasia.

Conflicts of Interest

Authors do not have any conflict of interest to disclose.

• References

• 1 Frigerio S, Lartey DA, D'Haens GR, Grootjans J.. The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms. Int J Mol Sci 2021; 22 (23): 12739 PMID: 34884543; PMCID: PMC8657929
• 2 Hirano T, Hirayama D, Wagatsuma K, Yamakawa T, Yokoyama Y, Nakase H.. Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis. Int J Mol Sci 2020; 21 (9): 3062 PMID: 32357539; PMCID: PMC7247693
• 3 Shah SC, Itzkowitz SH.. Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management. Gastroenterology 2022; 162 (3): 715-730.e3 Epub 2021 Oct 29. PMID: 34757143; PMCID: PMC9003896
• 4 Patel M, Horgan PG, McMillan DC, Edwards J.. NF-κB pathways in the development and progression of colorectal cancer. Transl Res 2018; 197: 43-56 Epub 2018 Mar 1. PMID: 29550444
• 5 Dutch Initiative on Crohn and Colitis (ICC). Wijnands AM, de Jong ME, Lutgens MWMD, Hoentjen F, Elias SG, Oldenburg B. Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis. Gastroenterology 2021; 160 (5): 1584-1598 Epub 2020 Dec 29. PMID: 33385426
• 6 Berkovich L, Gerber M, Katzav A, Kidron D, Avital S.. NF-kappa B expression in resected specimen of colonic cancer is higher compared to its expression in inflammatory bowel diseases and polyps. Sci Rep 2022; 12 (1): 16645 PMID: 36198850; PMCID: PMC9534908
• 7 Du Q, Zhang X, Cardinal J. et al. Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Research 2009; 69 (9): 3764-3771 PMID: 19383900
• 8 Greten FR, Grivennikov SI.. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity 2019; 51 (1): 27-41 PMID: 31315034; PMCID: PMC6831096
• 9 Pires BRB, Silva RCMC, Ferreira GM, Abdelhay E.. NF-kappaB: Two Sides of the Same Coin. Genes (Basel) 2018; 9 (1): 24 PMID: 29315242; PMCID: PMC5793177

Publication History

Article published online:
27 March 2025