Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer

M. Kalimutho, S. Di Cecilia, G. Del Vecchio Blanco, F. Roviello, P. Sileri, M. Cretella, A. Formosa, G. Corso, D. Marrelli, F. Pallone, G. Federici, S. Bernardini

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Abstract

Background: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker.Methods: The 5-aza-2′-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. Results: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P0.561.Conclusions:These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.

Original languageEnglish
Pages (from-to)1770-1778
Number of pages9
JournalBritish Journal of Cancer
Volume104
Issue number11
DOIs
Publication statusPublished - May 24 2011

Fingerprint

Colorectal Neoplasms
decitabine
Small Untranslated RNA
Messenger RNA
MicroRNAs
Feces
Methylation
Disease Progression
Survival Rate
Gene Expression
Polymerase Chain Reaction
Survival
DNA
Therapeutics

Keywords

  • CRC
  • faeces
  • methylation
  • miR-148a
  • miR-34b/c

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kalimutho, M., Di Cecilia, S., Del Vecchio Blanco, G., Roviello, F., Sileri, P., Cretella, M., ... Bernardini, S. (2011). Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer. British Journal of Cancer, 104(11), 1770-1778. https://doi.org/10.1038/bjc.2011.82

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer. / Kalimutho, M.; Di Cecilia, S.; Del Vecchio Blanco, G.; Roviello, F.; Sileri, P.; Cretella, M.; Formosa, A.; Corso, G.; Marrelli, D.; Pallone, F.; Federici, G.; Bernardini, S.

In: British Journal of Cancer, Vol. 104, No. 11, 24.05.2011, p. 1770-1778.

Research output: Contribution to journalArticle

Kalimutho, M, Di Cecilia, S, Del Vecchio Blanco, G, Roviello, F, Sileri, P, Cretella, M, Formosa, A, Corso, G, Marrelli, D, Pallone, F, Federici, G & Bernardini, S 2011, 'Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer', British Journal of Cancer, vol. 104, no. 11, pp. 1770-1778. https://doi.org/10.1038/bjc.2011.82
Kalimutho M, Di Cecilia S, Del Vecchio Blanco G, Roviello F, Sileri P, Cretella M et al. Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer. British Journal of Cancer. 2011 May 24;104(11):1770-1778. https://doi.org/10.1038/bjc.2011.82
Kalimutho, M. ; Di Cecilia, S. ; Del Vecchio Blanco, G. ; Roviello, F. ; Sileri, P. ; Cretella, M. ; Formosa, A. ; Corso, G. ; Marrelli, D. ; Pallone, F. ; Federici, G. ; Bernardini, S. / Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer. In: British Journal of Cancer. 2011 ; Vol. 104, No. 11. pp. 1770-1778.
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abstract = "Background: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker.Methods: The 5-aza-2′-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. Results: The miR-34b/c hypermethylation was found in 97.5{\%} (79 out of 82) of primary colorectal tumours, P0.0110. In 75{\%} (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16{\%} (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65{\%} (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65{\%}, P0.561.Conclusions:These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.",
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AU - Sileri, P.

AU - Cretella, M.

AU - Formosa, A.

AU - Corso, G.

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AU - Bernardini, S.

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N2 - Background: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker.Methods: The 5-aza-2′-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. Results: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P0.561.Conclusions:These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.

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