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SNP marker related to liver toxicity of platinum type chemotherapeutic medicines and applications thereof

A chemotherapeutic drug, liver toxicity technology, applied in the fields of genetic engineering and oncology

Active Publication Date: 2014-07-09
NANJING YIKE POPULATION HEALTH RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, there is no report on the application of SNPs in the auxiliary diagnosis of liver toxicity of platinum-based chemotherapy drugs. If SNPs that are susceptible to liver toxicity of platinum-based chemotherapy drugs can be screened out as biomarkers, and corresponding auxiliary diagnostic kits can be developed, it will be beneficial to my country. The status quo of auxiliary diagnosis of liver toxicity of platinum-based chemotherapy drugs will be a powerful impetus, and it will also open up a new way for its drug prevention and control

Method used

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  • SNP marker related to liver toxicity of platinum type chemotherapeutic medicines and applications thereof
  • SNP marker related to liver toxicity of platinum type chemotherapeutic medicines and applications thereof
  • SNP marker related to liver toxicity of platinum type chemotherapeutic medicines and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] The collection of embodiment 1 sample and the arrangement of sample data

[0065] The inventor collected a large number of blood samples from primary NSCLC patients from April 2005 to January 2011 from the Affiliated Cancer Hospital of Nanjing Medical University and the First Affiliated Hospital of Nanjing Medical University. A total of 334 genome-wide microarray scan samples meeting the following criteria were selected:

[0066] (1) New-onset NSCLC patients admitted to the hospital for the first time and confirmed by histopathology or cytology, whose diagnosis is confirmed by at least two pathologists according to the standards issued by the World Health Organization;

[0067] (2) All indicators of liver function tests before the first chemotherapy were normal;

[0068] (3) Receive 2 to 6 cycles of platinum-based chemotherapy; exclude NSCLC patients who received radiotherapy before or during chemotherapy;

[0069] (4) Have detailed evaluation information on liver tox...

Embodiment 2

[0071] Whole Genome Scanning of SNP in Example 2 Peripheral Blood DNA

[0072] Affymetrix6.0 chip detection was performed on the peripheral blood DNA of the 334 eligible NSCLC patients receiving platinum-based chemotherapy to obtain relevant results. The specific steps are:

[0073] 1. Add hemolysis reagent (that is, lysate, 40 parts) to the blood cells stored in the 2ml cryopreservation tube. Dilute to 2000ml, the same below), invert and mix completely before transferring.

[0074] 2. Removal of red blood cells: Fill the 5ml centrifuge tube to 4ml with hemolysis reagent, mix by inverting, centrifuge at 4000rpm for 10 minutes, and discard the supernatant. Add 4ml of hemolysis reagent to the precipitate, invert and wash again, centrifuge at 4000rpm for 10 minutes, and discard the supernatant.

[0075] 3. Extract DNA: Add 1ml of extract solution to the precipitate (each 300ml contains 122.5ml0.2M sodium chloride, 14.4ml0.5M ethylenediaminetetraacetic acid, 15ml10% sodium dode...

Embodiment 3

[0084] Example 3 Using the risk scoring method to further analyze the liver toxicity of SNP and platinum-based chemotherapy drugs

[0085] Based on the above results, the inventors selected the positively associated SNPs by comparing the genotype distribution frequencies of NSCLC patients with different degrees of liver toxicity, and used the regression coefficient of a single SNP in the whole genome scan sample as the weight to further obtain the risk score and draw ROC was used to evaluate the sensitivity and specificity of diagnosis, and then to evaluate the diagnostic ability of these SNPs for liver toxicity of platinum-based chemotherapy drugs. The combined analysis of 20 SNP markers found that these 20 SNPs separated NSCLC patients with hepatotoxicity from those without hepatotoxicity with a ROC of 73.5%, the sensitivity of the optimal cut-off point was 66.7%, and the specificity: 69.4% ( See figure 1 ).

[0086] 因此,本发明人证明了采用rs6681909、rs4140932、rs13131227、rs4446279、rs1...

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Abstract

The invention belongs to the fields of genetic engineering and oncology, and discloses an SNP marker related to liver toxicity of platinum type chemotherapeutic medicines and applications thereof. The marker is a composition of rs6681909, rs4140932, rs13131227, rs4446279, rs17053350, rs9402873, rs16878272, rs13267737, rs7008590, rs947853, rs2838566, rs1383888, rs9642723, rs3822296, rs2160046, rs10002931, rs10032941, rs6449138, rs1048037 and rs10086636. The marker and primer probes thereof can be used for preparing a diagnosis kit of the liver toxicity of platinum type chemotherapeutic medicines, and are good in sensitivity and specificity.

Description

field of invention [0001] The invention belongs to the fields of genetic engineering and oncology, and relates to a SNP marker related to liver toxicity of platinum chemotherapy drugs and an application thereof. Background technique [0002] Since the 1960s, platinum-based anticancer drugs represented by cisplatin have been widely used in the treatment of malignant tumors such as non-small cell lung cancer (NSCLC), and have become an indispensable drug in NSCLC chemotherapy. Platinum drugs are quickly distributed throughout the body after entering the human body, which can not only inhibit tumor growth and spread, but also kill distantly metastatic tumors, and have therapeutic effects on primary tumors, metastatic foci, and subclinical metastatic foci. However, due to the poor selectivity of platinum-based chemotherapeutic drugs to cells, while killing tumor cells, they also have a great destructive effect on normal cells, often causing some toxic and side effects. [0003]...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12N15/11
CPCC12Q1/6883C12Q2600/106C12Q2600/156
Inventor 沈洪兵胡志斌靳光付马红霞戴俊程江玥曹松玉
Owner NANJING YIKE POPULATION HEALTH RES INST CO LTD
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