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Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C.

Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, Shimotohno K - BMC Med Genomics (2010)

Bottom Line: The expression level of 470 mature miRNAs found their biopsy specimen, obtained prior to the combination therapy, were quantified using microarray analysis.We found that the expression level of 9 miRNAs were significantly different in the sustained virological response (SVR) and non-responder (NR) groups.The hepatic miRNA expression pattern that exists in CHC patients before combination therapy is associated with their therapeutic outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. ymurakami@genome.med.kyoto-u.ac.jp

ABSTRACT

Background: HCV infection frequently induces chronic liver diseases. The current standard treatment for chronic hepatitis (CH) C combines pegylated interferon (IFN) and ribavirin, and is less than ideal due to undesirable effects. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that control gene expression by degrading or suppressing the translation of target mRNAs. In this study we administered the standard combination treatment to CHC patients. We then examined their miRNA expression profiles in order to identify the miRNAs that were associated with each patient's drug response.

Methods: 99 CHC patients with no anti-viral therapy history were enrolled. The expression level of 470 mature miRNAs found their biopsy specimen, obtained prior to the combination therapy, were quantified using microarray analysis. The miRNA expression pattern was classified based on the final virological response to the combination therapy. Monte Carlo Cross Validation (MCCV) was used to validate the outcome of the prediction based on the miRNA expression profile.

Results: We found that the expression level of 9 miRNAs were significantly different in the sustained virological response (SVR) and non-responder (NR) groups. MCCV revealed an accuracy, sensitivity, and specificity of 70.5%, 76.5% and 63.3% in SVR and non-SVR and 70.0%, 67.5%, and 73.7% in relapse (R) and NR, respectively.

Conclusions: The hepatic miRNA expression pattern that exists in CHC patients before combination therapy is associated with their therapeutic outcome. This information can be utilized as a novel biomarker to predict drug response and can also be applied to developing novel anti-viral therapy for CHC patients.

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Clustering of CHC patients according to their final response to Peg-IFN and ribavirin combination therapy. Heatmap using miRNA differently expressed among SVR, R, and NR is shown (A: classification between NR and SVR, B: classification between NR and R, and C: classification between R and SVR, respectively). Vertical bars represent the miRNA genes and the horizontal bars represent the samples. Green bars reflect downregulated genes and red bars upregulated genes.
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Figure 2: Clustering of CHC patients according to their final response to Peg-IFN and ribavirin combination therapy. Heatmap using miRNA differently expressed among SVR, R, and NR is shown (A: classification between NR and SVR, B: classification between NR and R, and C: classification between R and SVR, respectively). Vertical bars represent the miRNA genes and the horizontal bars represent the samples. Green bars reflect downregulated genes and red bars upregulated genes.

Mentions: Unique miRNA expression patterns were established according to the final virological response (SVR, R, and NR) to the combination therapy (Figure 1). To isolate the miRNAs that were associated with the drug response to the combination therapy, we chose miRNAs which had ≥ 1.25 fold difference in the mean values of the gene expression level between at least two groups (p < 0.05). Unsupervised hierarchical clustering based on all the miRNAs spotted on the chip, revealed a marked, very distinct separation according to the patients' final response of the CHC liver tissue to the Peg-IFN and ribavirin combination therapy (Figure 2).


Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C.

Murakami Y, Tanaka M, Toyoda H, Hayashi K, Kuroda M, Tajima A, Shimotohno K - BMC Med Genomics (2010)

Clustering of CHC patients according to their final response to Peg-IFN and ribavirin combination therapy. Heatmap using miRNA differently expressed among SVR, R, and NR is shown (A: classification between NR and SVR, B: classification between NR and R, and C: classification between R and SVR, respectively). Vertical bars represent the miRNA genes and the horizontal bars represent the samples. Green bars reflect downregulated genes and red bars upregulated genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984584&req=5

Figure 2: Clustering of CHC patients according to their final response to Peg-IFN and ribavirin combination therapy. Heatmap using miRNA differently expressed among SVR, R, and NR is shown (A: classification between NR and SVR, B: classification between NR and R, and C: classification between R and SVR, respectively). Vertical bars represent the miRNA genes and the horizontal bars represent the samples. Green bars reflect downregulated genes and red bars upregulated genes.
Mentions: Unique miRNA expression patterns were established according to the final virological response (SVR, R, and NR) to the combination therapy (Figure 1). To isolate the miRNAs that were associated with the drug response to the combination therapy, we chose miRNAs which had ≥ 1.25 fold difference in the mean values of the gene expression level between at least two groups (p < 0.05). Unsupervised hierarchical clustering based on all the miRNAs spotted on the chip, revealed a marked, very distinct separation according to the patients' final response of the CHC liver tissue to the Peg-IFN and ribavirin combination therapy (Figure 2).

Bottom Line: The expression level of 470 mature miRNAs found their biopsy specimen, obtained prior to the combination therapy, were quantified using microarray analysis.We found that the expression level of 9 miRNAs were significantly different in the sustained virological response (SVR) and non-responder (NR) groups.The hepatic miRNA expression pattern that exists in CHC patients before combination therapy is associated with their therapeutic outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. ymurakami@genome.med.kyoto-u.ac.jp

ABSTRACT

Background: HCV infection frequently induces chronic liver diseases. The current standard treatment for chronic hepatitis (CH) C combines pegylated interferon (IFN) and ribavirin, and is less than ideal due to undesirable effects. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that control gene expression by degrading or suppressing the translation of target mRNAs. In this study we administered the standard combination treatment to CHC patients. We then examined their miRNA expression profiles in order to identify the miRNAs that were associated with each patient's drug response.

Methods: 99 CHC patients with no anti-viral therapy history were enrolled. The expression level of 470 mature miRNAs found their biopsy specimen, obtained prior to the combination therapy, were quantified using microarray analysis. The miRNA expression pattern was classified based on the final virological response to the combination therapy. Monte Carlo Cross Validation (MCCV) was used to validate the outcome of the prediction based on the miRNA expression profile.

Results: We found that the expression level of 9 miRNAs were significantly different in the sustained virological response (SVR) and non-responder (NR) groups. MCCV revealed an accuracy, sensitivity, and specificity of 70.5%, 76.5% and 63.3% in SVR and non-SVR and 70.0%, 67.5%, and 73.7% in relapse (R) and NR, respectively.

Conclusions: The hepatic miRNA expression pattern that exists in CHC patients before combination therapy is associated with their therapeutic outcome. This information can be utilized as a novel biomarker to predict drug response and can also be applied to developing novel anti-viral therapy for CHC patients.

Show MeSH
Related in: MedlinePlus