Decreasing Risk of Colorectal Cancer in Patients With Inflammatory Bowel Disease Over 30 Years

Jess, Tine; Simonsen, Jacob; Jørgensen, Kristian Tore; Pedersen, Bo Vest; Nielsen, Nete Munk

doi:10.1053/j.gastro.2012.04.016

Cited by 459 publications

(342 citation statements)

References 22 publications

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“…Increased levels of miR-20b have been reported in human cancers including lung cancer, gastric cancer and leukemias where miR-20b facilitates cellular adaption to normoxia and hypoxia in vitro by regulating the transcription factor hypoxia-inducible factor 1-alpha [51] . Therefore, it is possible that miR20b might be involved in the pathophysiology of colitisassociated colorectal cancer [52] .…”

Section: Discussionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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Author contributions: Coskun M and Bjerrum JT performed the experiments and data analysis, wrote the manuscript, and wrote the final revision of the article; Troelsen JT provided with analytical tools, intellectual input and advice; Olsen J provided with reagents and human tissue; Seidelin JB and Nielsen OH contributed to the conceptual design, drafting of the manuscript and revising it critically for important intellectual content; all authors approved the final submitted manuscript. Abstract AIM: To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIM-CA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-Whitney U test. In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Using in silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.

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Section: Discussionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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“…In a new population-based chort study encompassing 47347 Danish patients with IBD, 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation (Jess et al, 2012). The authors concluded that the overall risk of CRC among patients with UC was comparable with that of the general population (relative risk, 1.7; 95% confidence interval, 0.95-1.21).…”

Section: Roles Of Emt In the Pathogenesis Of Colorectal Cancer Promotmentioning

confidence: 99%

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

Zhu¹,

Gao²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

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“…Initially early diagnosis was associated with increased risk [16,19], while other work has demonstrated the opposite effect, with those who are elderly at diagnosis at higher risk [62,63]. Male gender also increase the risk Primary sclerosing cholangitis confers a 4-fold increase in risk of CRC development in UC patients [17,[64][65][66], with the increased risk persisting following liver transplantation [67,68].…”

Section: Risk Factorsmentioning

confidence: 99%

“…However, care of UC patients has changed a great deal in the intervening years, and along with changes in the methodology of patient recruitment, this has led to a change in reported prevalence. From 1979 to 1988 the relative risk of CRC in UC was noted to be 1.34 with that decreasing to 0.57 between 1999 and 2008 [17], and similarly incidence rates have decreased from 4.29/1000 PYD in the 1950s to 1.09/1000 in the first part of the 2000s [18]. Moreover, incidence rates in the first, second, and third decades of disease have decreased to 1.01/1000, 3.75/1000 and 5.85/1000 PYD respectively [18].…”

Section: Epidemiologymentioning

confidence: 99%

“…That is, in those CD subjects with extensive colitis, there appears to be somewhat of an increased risk, while those with disease limited to the small bowel appear to be at a baseline risk [19][20][21]. When all phenotypes of Crohn's disease are included, some studies place the relative risk of CRC between 2 and 3 [22][23][24], whereas others do not demonstrate any increased risk [17,25,26].…”

Section: Risk Factorsmentioning

confidence: 99%

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Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

Karmali¹

2015

Surgery Curr Res

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Decreasing Risk of Colorectal Cancer in Patients With Inflammatory Bowel Disease Over 30 Years

Cited by 459 publications

References 22 publications

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

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Decreasing Risk of Colorectal Cancer in Patients With Inflammatory Bowel Disease Over 30 Years

Cited by 459 publications

References 22 publications

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

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Product

Resources

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miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis