Method for predicting sensitivity to vascular endothelial growth factor receptor inhibitor

A growth factor receptor, vascular endothelial technology, applied in the field of predicting the sensitivity of liver cancer patients to vascular endothelial growth factor receptor inhibitor therapy, can solve the threshold and diagnostic performance of not properly assessing resistance or sensitivity, can not Guarantee the treatment effect of guidelines and other issues, and achieve high accuracy and high mRNA levels

Inactive Publication Date: 2017-09-29
CBSBIOSCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

That is, current guidelines for the treatment of HCC are not based on the molecular characteristics of the tumor, so there is a limitation that the treatment effect of the guidelines cannot be guaranteed
In addition, although some genes known as biomarkers exist, the thresholds and diagnostic performance for predicting resistance or sensitivity of these genes have not been properly assessed, so additional studies are needed to demonstrate the clinical usefulness of these genes

Method used

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  • Method for predicting sensitivity to vascular endothelial growth factor receptor inhibitor
  • Method for predicting sensitivity to vascular endothelial growth factor receptor inhibitor
  • Method for predicting sensitivity to vascular endothelial growth factor receptor inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1: RNA extraction and cDNA synthesis

[0062] Thirty-one patients with liver cancer who were diagnosed with liver cancer, underwent liver resection or liver transplantation, showed recurrence of liver cancer, and received Nexavar (Sorafenib) at Ajou University Medical Center, Korea University Annam Hospital, and Keimyung University Dongsan Medical Center Treatment, liver cancer tissues were obtained with informed consent. RNA was extracted from each tissue in the following manner, from which cDNA was synthesized.

[0063] Total RNA was extracted from liver cancer tissues and surrounding normal tissues using the RNeasy Mini Kit (Qiagen, Germany) according to the manufacturer's instructions. The extracted total RNA was quantified using Bioanalyzer 2100 (Agilent Technologies, USA). During the extraction step, RNA extracts are treated with DNase I to remove genomic DNA. Each sample containing 4 μg of total RNA was incubated with 2 μl of 1 μM oligo d(T)18 primer...

Embodiment 2

[0064] Example 2: Quantitative real-time PCR

[0065] In order to measure the mRNA expression level of mTOR, VEGFR2, PDGFRβ, FGFR1, cKIT, EGFR or cRAF of each cDNA sample obtained in Example 1, according to the manufacturer's instructions, using PRISM 7900HT (Applied Biosystems, USA) by real-time PCR amplification Gene markers shown in Table 1 below.

[0066] Real-time PCR analysis was performed using a total volume of 10 μl consisting of 5 μl of 2x TaqMan Gene Expression Master Mix (Applied Biosystems, USA), 1 μl each of 5 μM forward and reverse primers, 1 μl of 1 μM probe (Genotech, Korea) and 2 μl of cDNA (the same amount of water as a control). PCR amplification was performed by denaturation at 95°C for 10 minutes, followed by a cycling reaction consisting of denaturation at 95°C for 15 seconds and synthesis at 60°C for 1 minute. Primer and probe sequences were designed using Primer Express 3.0 (Applied Biosystems, USA), and all probe sequences were labeled with FAM at...

Embodiment 3

[0074] Embodiment 3: statistical analysis

[0075] Using the expression levels of the markers obtained in Example 2 (2 -ΔCt ), a total of four statistical analyzes (ie individual gene expression distribution analysis, ROC curve analysis, treatment benefit score analysis and ROC curve analysis of treatment benefit score) were performed in the following manner.

[0076] (1) Analysis of individual gene expression distribution

[0077] In order to detect the therapeutic effect of Sorafenib and the expression level of a single marker (2 -ΔCT ), the expression levels and distributions of seven individual markers were analyzed for Sorafenib responders and Sorafenib non-responders respectively, and the analysis results are shown in figure 1 .

[0078] figure 1 Results of analysis of mRNA expression levels of seven genes (ie, mTOR, VEGFR2, PDGFRβ, FGFR1, cKIT, EGFR, and cRAF) in responders and non-responders are shown.

[0079] When expression of each of these markers showed: ...

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Abstract

The invention discloses a method for predicting sensitivity to vascular endothelial growth factor receptor inhibitor. The present invention relates to a method for predicting the sensitivity to treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors, by using a biomarker. An effective means and anticancer therapy for cancer treatment of liver cancer are selected by predicting the effect of treatment with VEGFR inhibitors on liver cancer patients through the present invention, thereby increasing the treatment effect and minimizing the side effects of liver cancer treatment.

Description

technical field [0001] The invention relates to a method for predicting the sensitivity of liver cancer patients to the treatment of vascular endothelial growth factor receptor inhibitors, so as to determine whether the patients can accept the therapeutic effect from the treatment. Background technique [0002] Cancer is one of the deadliest diseases threatening human health. In the United States alone, cancer affects nearly 1.3 million new patients each year and is the second leading cause of death after heart disease, accounting for about 1 in 4 deaths. Although there have been significant advances in the medical treatment of certain cancers, the overall 5-year survival rate for all cancers has only improved by about 10% over the past 20 years. Furthermore, cancer or malignant tumors metastasize and grow rapidly in an uncontrolled manner, making timely detection and treatment very difficult. [0003] Depending on the type of cancer, patients typically have several treatm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q1/6886C12Q2600/158C12Q2600/106A61K31/44A61P1/16A61P35/00C12Q1/6844G01N33/15C12Q2600/136
Inventor 朴真永文永镐权正熙金延洙金周贤崔德柱
Owner CBSBIOSCI
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