MicroRNAs in colorectal cancer metastasis

Krijger, Inge de; Mekenkamp, L.; Punt, Cornelis J.A.; Nagtegaal, Irıs D.

doi:10.1002/path.2922

Cited by 111 publications

(96 citation statements)

References 76 publications

(99 reference statements)

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“…Therefore, prognostic markers, which identify patients with high risk of recurrence and metastasis may have an important impact on the clinical management of patients with colon cancer. Within the last years, several prognostic markers associated with distant spread could be identified, and more recently, the expression of several miRNAs, such as miR-17-92 and miR-21, was associated with metastatic disease in colon cancer (3).…”

Section: Introductionmentioning

confidence: 99%

Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer

Siemens¹,

Neumann²,

Jackstadt³

et al. 2013

Clinical Cancer Research

132

105

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Purpose: Here, we determined whether epigenetic inactivation of miR-34a and miR-34b/c genes may serve as a prognostic marker for distant metastases in colon cancer.Experimental Design: Using a case-control study design of 94 primary colon cancer samples with and without liver metastases, we determined CpG methylation frequencies of miR-34a and miR-34b/c promoters, expression of miR-34a, and its targets c-Met, Snail, and b-catenin and their prognostic value.Results: miR-34a methylation was detected in 45.1% (n ¼ 42 of 93) of the samples and strongly associated with metastases to the liver (P ¼ 0.003) and lymph nodes (P ¼ 0.006). miR-34b/c methylation was detected in 91.9% of the samples (n ¼ 79/86). A significant inverse correlation between miR-34a methylation and expression of mature miR-34a (P ¼ 0.018) was detected. Decreased miR-34a expression was associated with upregulation of c-Met, Snail, and b-catenin protein levels (P ¼ 0.031, 0.132, and 0.004), which were associated with distant metastases (P ¼ 0.001, 0.017, and 0.005). In a confounder-adjusted multivariate regression model miR-34a methylation, high c-Met and b-catenin levels provided the most significant prognostic information about metastases to the liver (P ¼ 0.014, 0.031, and 0.058) and matched pairs showed a higher prevalence of these risk factors in the samples with distant spread (P ¼ 0.029). Finally, we obtained statistical evidence indicating that the simultaneous detection of these three markers has the highest prognostic value.Conclusions: Silencing of miR-34a and upregulation of c-Met, Snail, and b-catenin expression is associated with liver metastases of colon cancer. Detection of miR-34a silencing in resected primary colon cancer may be of prognostic value, especially in combination with detection of c-Met and b-catenin expression.

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Section: Introductionmentioning

confidence: 99%

Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer

Siemens¹,

Neumann²,

Jackstadt³

et al. 2013

Clinical Cancer Research

132

105

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“…As discussed by de Krijger and colleagues (14), a similar profile for patients with colon cancer is warranted as the development of distant metastases mainly accounts for the high lethality rates of colon cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Classifier and Nomogram for Metastasis Prediction in Colon Cancer

Goossens-Beumer

Derr

Buermans

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Colon cancer prognosis and treatment are currently based on a classification system still showing large heterogeneity in clinical outcome, especially in TNM stages II and III. Prognostic biomarkers for metastasis risk are warranted as development of distant recurrent disease mainly accounts for the high lethality rates of colon cancer. miRNAs have been proposed as potential biomarkers for cancer. Furthermore, a verified standard for normalization of the amount of input material in PCR-based relative quantification of miRNA expression is lacking.Methods: A selection of frozen tumor specimens from two independent patient cohorts with TNM stage II-III microsatellite stable primary adenocarcinomas was used for laser capture microdissection. Next-generation sequencing was performed on small RNAs isolated from colorectal tumors from the Dutch cohort (N ¼ 50). Differential expression analysis, comparing in metastasized and nonmetastasized tumors, identified prognostic miRNAs.

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“…miRNAs are frequently deregulated in many types of human cancers and play critical roles in tumorigenesis, serving as tumor suppressors or oncogenes (21,22). Recent studies have shown that several miRNAs, such as miR-146a, miR-155, and miR-21, are involved in H. pylori-induced infection (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

Feng

Wang

Zeng

et al. 2013

Molecular Cancer Research

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Helicobacter pylori (H. pylori) infections are strongly implicated in human gastric mucosa-associated diseases. Forkhead box M1 (FoxM1), a key positive regulator of cell proliferation, is overexpressed in gastric cancer. MicroRNAs are important post-transcriptional regulators of gene expression. In this study, the effects of H. pylori infection on FoxM1 expression and possible mechanisms of carcinogenesis were explored. The expression of FoxM1 was gradually increased in human gastric specimens from inflammation to cancer. FoxM1 upregulation was time-and concentration-dependent in gastric epithelial-derived cell lines infected with H. pylori. CagA, a key virulence factor of H. pylori, was associated with increased FoxM1 expression.

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MicroRNAs in colorectal cancer metastasis

Cited by 111 publications

References 76 publications

Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer

Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer

MicroRNA Classifier and Nomogram for Metastasis Prediction in Colon Cancer

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

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