Risk of Colon Cancer and Recommended Surveillance Strategies in Patients with Ulcerative Colitis

Rabbenou, Wendy; Ullman, Thomas

doi:10.1016/j.gtc.2020.08.005

Cited by 18 publications

(16 citation statements)

References 81 publications

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“…In fact, patients with longstanding and extensive IBD are at increased risk of CRC [61,62]. In UC, this malignant transformation is believed to result from a chronic inflammation-dysplasia-carcinoma sequence [63]. Current practice is to perform surveillance examinations every 1-3 years for detection and removal of lesions.…”

Section: Involvement Of Reg Family Proteins In Inflammation-associated Carcinogenesismentioning

confidence: 99%

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

Sun

Wang

Hui

et al. 2021

IJMS

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Regenerating gene (REG) family proteins serve as multifunctional secretory molecules with trophic, antiapoptotic, anti-inflammatory, antimicrobial and probably immuno-regulatory effects. Since their discovery, accumulating evidence has clarified the potential roles of the REG family in the occurrence, progression and development of a wide range of inflammatory and inflammation-associated diseases of the gastrointestinal (GI) tract. However, significant gaps still exist due to the undefined nature of certain receptors, regulatory signaling pathways and possible interactions among distinct Reg members. In this narrative review, we first describe the structural features, distribution pattern and purported regulatory mechanisms of REG family proteins. Furthermore, we summarize the established and proposed roles of REG proteins in the pathogenesis of various inflammation-associated pathologies of the GI tract and the body as a whole, focusing particularly on carcinogenesis in the ulcerative colitis—colitic cancer sequence and gastric cancer. Finally, the clinical relevance of REG products in the context of diagnosis, treatment and prognostication are also discussed in detail. The current evidence suggests a need to better understanding the versatile roles of Reg family proteins in the pathogenesis of inflammatory-associated diseases, and their broadened future usage as therapeutic targets and prognostic biomarkers is anticipated.

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Section: Involvement Of Reg Family Proteins In Inflammation-associated Carcinogenesismentioning

confidence: 99%

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

Sun

Wang

Hui

et al. 2021

IJMS

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“… 15 An abnormal immune response is an important mechanism for the occurrence and development of colon cancer. 20 , 21 Immune response-related indicators have shown the application value of evaluating the prognosis of colon cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Novel Inflammatory Response-Related Gene Signature for the Prognosis of Colon Cancer

Yue¹,

Wu²,

Qi³

et al. 2021

JIR

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Purpose The inflammatory response plays a crucial role in the occurrence and development of colon cancer. In this study, we aimed to explore a novel prognostic model for patients with colon cancer (COAD) based on inflammatory response-related genes. Methods Inflammatory response-related genes were obtained from Molecular Signatures database. Univariate and multivariate Cox regression analyses were used for model construction based on TCGA dataset. GSE39582 dataset and qRT-PCR dataset were used for validation. Gene set variation analysis and gene set enrichment analysis were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT. Immunohistochemistry analysis and experiments were used to explore the function of genes in model. Results In this study, a novel prognostic signature was identified using stepwise Cox proportional hazards regression analysis based on TCGA dataset. The results were subsequently validated in 562 patients from GSE39582 and a qRT-PCR data set from 70 tumor samples. Functional analysis indicated that the tumor microenvironment and immune cell infiltrate were different between high- and low-risk groups. Additionally, IHC results showed that the protein levels of prognostic genes were significantly different between COAD tissues and adjacent non-tumorous tissues, and prognostic genes could regulate the malignant phenotype of COAD cells. Conclusion Overall, the inflammation-related gene signature can be used for prognostic prediction in patients with COAD.

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“…Moreover, it is well known that chronic inflammation can lead to cancer development ( Greten and Grivennikov, 2019 ). In particular, UC increases the risk to develop colorectal cancer ( Rabbenou and Ullman, 2020 ). Arpin downregulation has been associated with the development of different cancer types, including colon cancer ( Lomakina et al, 2016 ; Li T. et al, 2017 ; Li Y. et al, 2017 ; Zhang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity

Chánez-Paredes

Montoya-García

Castro-Ochoa

et al. 2021

Front. Cell Dev. Biol.

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The intestinal epithelial barrier (IEB) depends on stable interepithelial protein complexes such as tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton. During inflammation, the IEB is compromised due to TJ protein internalization and actin remodeling. An important actin regulator is the actin-related protein 2/3 (Arp2/3) complex, which induces actin branching. Activation of Arp2/3 by nucleation-promoting factors is required for the formation of epithelial monolayers, but little is known about the relevance of Arp2/3 inhibition and endogenous Arp2/3 inhibitory proteins for IEB regulation. We found that the recently identified Arp2/3 inhibitory protein arpin was strongly expressed in intestinal epithelial cells. Arpin expression decreased in response to tumor necrosis factor (TNF)α and interferon (IFN)γ treatment, whereas the expression of gadkin and protein interacting with protein C-kinase α-subunit 1 (PICK1), other Arp2/3 inhibitors, remained unchanged. Of note, arpin coprecipitated with the TJ proteins occludin and claudin-1 and the AJ protein E-cadherin. Arpin depletion altered the architecture of both AJ and TJ, increased actin filament content and actomyosin contractility, and significantly increased epithelial permeability, demonstrating that arpin is indeed required for maintaining IEB integrity. During experimental colitis in mice, arpin expression was also decreased. Analyzing colon tissues from ulcerative colitis patients by Western blot, we found different arpin levels with overall no significant changes. However, in acutely inflamed areas, arpin was significantly reduced compared to non-inflamed areas. Importantly, patients receiving mesalazine had significantly higher arpin levels than untreated patients. As arpin depletion (theoretically meaning more active Arp2/3) increased permeability, we wanted to know whether Arp2/3 inhibition would show the opposite. Indeed, the specific Arp2/3 inhibitor CK666 ameliorated TNFα/IFNγ-induced permeability in established Caco-2 monolayers by preventing TJ disruption. CK666 treatment also attenuated colitis development, colon tissue damage, TJ disruption, and permeability in dextran sulphate sodium (DSS)-treated mice. Our results demonstrate that loss of arpin triggers IEB dysfunction during inflammation and that low arpin levels can be considered a novel hallmark of acute inflammation.

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Risk of Colon Cancer and Recommended Surveillance Strategies in Patients with Ulcerative Colitis

Cited by 18 publications

References 81 publications

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

Identification and Validation of a Novel Inflammatory Response-Related Gene Signature for the Prognosis of Colon Cancer

The Arp2/3 Inhibitory Protein Arpin Is Required for Intestinal Epithelial Barrier Integrity

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