Detection of miR-34a promoter methylation in combination with elevated expression of c-Met and β-catenin predicts distant metastasis of colon cancer
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 determi...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2013
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| In: |
Clinical cancer research
Year: 2013, Jahrgang: 19, Heft: 3, Pages: 710-720 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-12-1703 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1158/1078-0432.CCR-12-1703 Verlag, kostenfrei, Volltext: http://clincancerres.aacrjournals.org/content/19/3/710 
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| Verfasserangaben: | Helge Siemens, Jens Neumann, Rene Jackstadt, Ulrich Mansmann, David Horst, Thomas Kirchner, and Heiko Hermeking |
| Zusammenfassung: | 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 β-catenin and their prognostic value. Results: miR-34a methylation was detected in 45.1% (n = 42 of 93) of the samples and strongly associated with metastases to the liver (P = 0.003) and lymph nodes (P = 0.006). miR-34b/c methylation was detected in 91.9% of the samples (n = 79/86). A significant inverse correlation between miR-34a methylation and expression of mature miR-34a (P = 0.018) was detected. Decreased miR-34a expression was associated with upregulation of c-Met, Snail, and β-catenin protein levels (P = 0.031, 0.132, and 0.004), which were associated with distant metastases (P = 0.001, 0.017, and 0.005). In a confounder-adjusted multivariate regression model miR-34a methylation, high c-Met and β-catenin levels provided the most significant prognostic information about metastases to the liver (P = 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 = 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 β-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 β-catenin expression. Clin Cancer Res; 19(3); 710-20. ©2012 AACR. |
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| Beschreibung: | Published first December 14, 2012 Gesehen am 27.08.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-12-1703 |