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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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Real-time qPCR validation of the seven miRNAs. Each column represents the relative amount of miRNAs normalized to expression level of U18. The data shown were means+SD of three independent experiments. Asterisk indicates a significant difference of p < 0.05 (*) or p < 0.01 (**).
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Figure 3: Real-time qPCR validation of the seven miRNAs. Each column represents the relative amount of miRNAs normalized to expression level of U18. The data shown were means+SD of three independent experiments. Asterisk indicates a significant difference of p < 0.05 (*) or p < 0.01 (**).

Mentions: The three miRNAs (miR-18a, miR-27b, and miR-422b) with the smallest difference of fold change between NR and SVR groups and four miRNA (miR-143, miR-145, miR-34b, and miR-378) with the largest difference of fold change between NR and SVR groups were chosen to confirm the microarray results using stem-loop based real-time qPCR. The result of real-time qPCR corresponded to the result from the microarray analysis (Figure 3).


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)

Real-time qPCR validation of the seven miRNAs. Each column represents the relative amount of miRNAs normalized to expression level of U18. The data shown were means+SD of three independent experiments. Asterisk indicates a significant difference of p < 0.05 (*) or p < 0.01 (**).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Real-time qPCR validation of the seven miRNAs. Each column represents the relative amount of miRNAs normalized to expression level of U18. The data shown were means+SD of three independent experiments. Asterisk indicates a significant difference of p < 0.05 (*) or p < 0.01 (**).
Mentions: The three miRNAs (miR-18a, miR-27b, and miR-422b) with the smallest difference of fold change between NR and SVR groups and four miRNA (miR-143, miR-145, miR-34b, and miR-378) with the largest difference of fold change between NR and SVR groups were chosen to confirm the microarray results using stem-loop based real-time qPCR. The result of real-time qPCR corresponded to the result from the microarray analysis (Figure 3).

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