Loss of enteric neuronal
            <i>Ndrg4</i>
            promotes colorectal cancer via increased release of Nid1 and Fbln2

Vaes, Nathalie; Schonkeren, Simone L.; Rademakers, Glenn; Holland, Amy Marie; Koch, Alexander; Gijbels, Marion J.J.; Keulers, Tom G.; Wit, Meike de; Moonen, Laura; Meer, Jaleesa R M van der; Boezem, E van den; Wolfs, Tim G. A. M.; Threadgill, David W.; Demmers, Jeroen; Fijneman, Remond J.A.; Jiménez, Connie R.; Berghe, Pieter Vanden; Smits, Kim M.; Rouschop, Kasper M.A.; Boesmans, Werend; Hofstra, Robert M.W.; Melotte, Veerle

doi:10.15252/embr.202051913

Cited by 22 publications

(14 citation statements)

References 71 publications

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“…The protein sequences encoded by this family have a 52-65% homology and are highly conserved in the evolution of various species (43), with α/β hydrolase folding. Previously, researchers have identified NDRG4 promoter CpG island methylation as a potential and one of the most accurate marker for CRC detection (44), and this has been verified by an independent study (45).…”

Section: Screening and Early Detection Markersmentioning

confidence: 72%

Value of methylation markers in colorectal cancer (Review)

Kong

2021

Oncol Rep

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Colorectal cancer (CRC) is a multifactorial and multistage process that occurs due to both genetic and epigenetic variations in normal epithelial cells. Analysis of the CRC epigenome has revealed that almost all CRC types have a large number of abnormally methylated genes. Hypermethylation of cell-free DNA from CRC in the blood or stool is considered as a potential non-invasive cancer biomarker, and various methylation markers have shown high sensitivity and specificity. The aim of the present review was to examine potential methylation markers in CRC that have been used or are expected to be used in the clinical setting, focusing on their screening, predictive, prognostic and therapeutic roles in CRC.

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Section: Screening and Early Detection Markersmentioning

confidence: 72%

Value of methylation markers in colorectal cancer (Review)

Kong

2021

Oncol Rep

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“…Interestingly, ADAMTS-12 was found to promote tumor development in breast cancer cells lacking FBLN2 by regulating metalloproteinase ( Fontanil et al, 2014 ). In contrast, another study found that FBLN2 promoted tumor growth by interacting with activated β integrin receptor in CRC ( Vaes et al, 2021 ). Consistent with the above finding, high expression level of these two genes ( FBLN2 and HTRA3 ) was linked to worse prognosis in colon cancer ( Figures 9E,F ), and FBLN2 was found to be significantly differentially expressed in CC ( Figure 9H ).…”

Section: Discussionmentioning

confidence: 95%

A Novel Quantification System Combining iTRAQ Technology and Multi-Omics Assessment to Predict Prognosis and Immunotherapy Efficacy in Colon Cancer

Xia

Guo

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Colon cancer is one of the most common cancer types, although it has certain unique genetic features. This study aimed to develop a unique score for assessing prognosis and immunotherapy efficacy using integrated multi-omics analysis.Methods: Isobaric tagging for relative and absolute quantification (iTRAQ) based proteomic analysis was used to screen differentially expressed proteins (DEP) between tumor and normal samples. DEP mRNA obtained from TCGA were clustered into different categories to show landscape-related prognosis and function. Following that, DEG was extracted from DEP mRNA, and the DEP-related score (DEPRS) was constructed to investigate the difference in immunotherapy prognosis and sensitivity. Finally, WCGNA, random forest, and artificial neural networks were used to screen for key genes. The prognostic value and protein level of these genes were validated.Results: A total of 243 DEPs were identified through iTRAQ analysis, and the corresponding DEP mRNA was clustered into three. Following a series of tests, 1,577 DEGs were identified from overlapped DEP mRNA clusters and were classified into three gene clusters. The two types of clusters described above shared comparable characteristics in terms of prognosis and function. Then, it was established that a high DEPRS indicated a poor prognosis and DEPRS had significant associations with TMB, MSI status, and immunotherapeutic response. Finally, the key genes HART3 and FBLN2 were identified and were found to be implicated in immunotherapy and prognosis.Conclusion: The development of a DEPRS based on multi-omics analysis will aid in improving our understanding of colon cancer and guiding a more effective immunotherapy strategy. DEPRS and key genes are used as biomarkers in the clinical evaluation of patients.

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“…N-Myc Downstream-Regulated Gene 4 (NDRG4), expressed within nervous system structures throughout the body, but predominantly studied in the brain and heart, was proven to be expressed explicitly in enteric neurons in a study using tissues from NDRG4 wild-type, heterozygous, and knockout mice and humans; immunoreactivity was restricted to the enteric nervous system (ENS) [ 58 ]. A recent study aiming to identify whether the ENS, via NDRG4, affects intestinal tumorigenesis showed that Ndrg4 knockdown in CRC models and in an indirect co-culture of primary enteric nervous system (ENS) cells was associated with enlarged intestinal adenoma development—the organoid growth being boosted by the Ndrg4−/− ENS cell secretome—the ENS, via loss of Ndrg4, being involved in colorectal pathogenesis [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

Anghel

Ioniță-Mîndrican

Luca

et al. 2021

Cancers

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In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science® Core Collection, MEDLINE® and Scopus® databases were searched for original articles published in peer-reviewed journals with the specific keywords “colorectal cancer”, “early detection”, “early-stage colorectal cancer”, “epigenetics”, “biomarkers”, “DNA methylation biomarkers”, “stool or blood or tissue or biopsy”, “NDRG4”, “BMP3”, “SEPT9”, and “SDC2”. Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test—the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.

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Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2

Cited by 22 publications

References 71 publications

Value of methylation markers in colorectal cancer (Review)

Value of methylation markers in colorectal cancer (Review)

A Novel Quantification System Combining iTRAQ Technology and Multi-Omics Assessment to Predict Prognosis and Immunotherapy Efficacy in Colon Cancer

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

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