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Blood plasma miRNA spectrum and detection kit used for predicting chronic hepatitis b curative effect of interferon

A technology for chronic hepatitis B and interferon, applied in the fields of molecular biology and medicine, can solve problems such as limited prediction ability, and achieve the effects of low cost, convenient detection method, and reduced treatment cost

Inactive Publication Date: 2012-04-04
SHANGHAI PUBLIC HEALTH CLINICAL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the predictive ability of current indicators is limited, and there is an urgent need for a molecular marker that can be detected in blood and has high predictive accuracy

Method used

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  • Blood plasma miRNA spectrum and detection kit used for predicting chronic hepatitis b curative effect of interferon
  • Blood plasma miRNA spectrum and detection kit used for predicting chronic hepatitis b curative effect of interferon
  • Blood plasma miRNA spectrum and detection kit used for predicting chronic hepatitis b curative effect of interferon

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Detection of miRNA expression profiles

[0026] 1. Experimental materials:

[0027] The invention obtains plasma and serum samples from 94 cases of chronic hepatitis B patients receiving long-acting interferon and common interferon. This study was approved by the Ethics Committee, and all patients signed informed consent. The training set included 66 HBV patients who received EG-IFN α2a (180μg / week) or PEG-IFN α2b (100μg / week), and the test set included 28 patients who received common interferon (IFN-α2b or IFN-α1b, 3-5MU / qod) HBV patients. The basic clinical data of the enrolled patients are shown in Table 1, 81.9% of them were positive for e antigen, and the average viral load was 7.05 log 10 copies / ml. Inclusion and exclusion criteria: The enrolled HBV patients had not received nucleoside analogs or interferon therapy 6 months before starting treatment, and the viral load was 5×10 4copies / ml and above, abnormal liver alanine aminotransferase (>1.0 U...

Embodiment 2

[0040] Embodiment 2: Statistical analysis and establishment of forecasting model

[0041] one. experiment method:

[0042] Maximum Relevance Minimum Redundancy Analysis (mRMR)

[0043] The maximum correlation minimum redundancy analysis was first developed by Peng et al. To evaluate and analyze feature values, we used the (mRMR) method to evaluate the relevance of each miRNA to patient efficacy and redundancy to other miRNAs. A miRNA with higher correlation and lower redundancy can be considered as a good miRNA signature. To measure correlation and redundancy, mutual information (MI) is used. Finally, each miRNA gets a Maxrel score according to its association.

[0044] Nearest Neighbor Classification Algorithm (NN)

[0045] In the present invention, the nearest neighbor classification algorithm (NN) is used as the prediction algorithm. The NN algorithm is a simple but very effective machine learning method that is widely used in various classification problems. I...

Embodiment 3

[0060] Example 3 Prediction of 28 routine samples treated with common interferon

[0061] The present invention further tested whether the prediction model of these ten miRNAs could effectively distinguish the initial virological response in a test set consisting of 28 patients. As shown in Table 1, the basic clinical data of the test set and the training set are similar, except that the patients in the test set received common interferon treatment. Since different interferon preparations will cause differences in the effective drug concentration in vivo, this may affect the performance of the prediction. Nevertheless, we still get an overall prediction accuracy of 60.7% on the training set.

[0062] Comparison of miRNA prediction models with known factors associated with efficacy

[0063] The present invention further carried out univariate and multivariate Logistic regression analysis to evaluate whether the miRNA model is an independent predictor related to curative eff...

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Abstract

The invention belongs to the fields of molecular biology and medical science, and provides a blood plasma miRNA spectrum used for predicting the chronic hepatitis b curative effect of an interferon. The miRNA spectrum comprises one or a plurality of miRNA in SEQ ID No.1-10. The invention also provides a corresponding high-efficiency and low-cost kit, a detection chip and a detection method. The method and the kit provided by the invention are used for detecting miRNA levels in blood plasma and blood serum. The method and the kit are suitable to be used clinically for determining the effectiveness of an interferon. Compared to other known related factors, the expression spectrum is an independent prediction factor. The combination of the expression spectrum and HBV drug-resistance mutation analysis assists in the practice of individualized treatment schemes, and finally in reducing treatment costs and improving complete response proportions.

Description

technical field [0001] The present invention relates to the fields of molecular biology and medicine. More specifically, it involves plasma miRNA expression levels to predict the efficacy of interferon therapy for chronic hepatitis B. The present invention also relates to methods and kits for detecting miRNA levels. Background technique [0002] Hepatitis B virus (HBV) infection causes chronic liver disease and significantly increases the risk of hepatocellular carcinoma. Although HBsAg recombinant antigen vaccines have been widely used to prevent infection, HBV infection remains an important health problem in countries around the world. Interferon α and nucleoside analogs, such as lamivudine, adefovir, entecavir, telbivudine, etc., are the main drugs for the treatment of HBV infection. Interferon therapy can usually only achieve complete response in limited patients, and it is easy to relapse after discontinuation of treatment. In recent years, the application of pegyla...

Claims

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Application Information

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IPC IPC(8): C12Q1/68C12N15/113
CPCC12Q2600/178C12Q1/6883C12Q1/706C12Q2600/158C12Q2600/106
Inventor 袁正宏张小楠邬敏陈良张继明张欣欣张占卿吴景迪王介非陈晓蓉黄涛
Owner SHANGHAI PUBLIC HEALTH CLINICAL CENT
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