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Application of DKK1 as diagnostic marker

A use and technology of diagnostic reagents, applied in the field of DKK1 as a diagnostic marker, can solve the problem of unclear diagnostic ability of hepatocellular carcinoma or small hepatocellular carcinoma

Inactive Publication Date: 2014-01-01
SHANGHAI INST OF ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] However, the current clinical significance of serum DKK1 for hepatocellular carcinoma, especially its ability to diagnose alpha-fetoprotein-negative hepatocellular carcinoma, the ability to differentially diagnose hepatocellular carcinoma and alpha-fetoprotein-positive chronic liver disease, and early hepatocellular carcinoma or small liver disease. The diagnostic ability of cell carcinoma is unclear

Method used

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  • Application of DKK1 as diagnostic marker

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Experimental program
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Embodiment approach

[0091] As an embodiment of the present invention, the reagent is an anti-DKK1 antibody; more specifically, it is a monoclonal antibody or a polyclonal antibody.

[0092] Antibodies of the present invention can be prepared by various techniques known to those skilled in the art. For example, purified antigen can be administered to animals such as rabbits, mice, rats, etc. to induce polyclonal antibody production. Various adjuvants can be used to enhance the immune response, including but not limited to Freund's adjuvant and the like.

[0093] Antibodies of the invention may also be monoclonal antibodies. Such monoclonal antibodies can be prepared using hybridoma technology.

[0094] The antibody can be used in immunochemical techniques to detect the level of DKK1 in the specimen, so as to diagnose hepatocellular carcinoma, especially alpha-fetoprotein-negative hepatocellular carcinoma, early hepatocellular carcinoma or small hepatocellular carcinoma, or to judge the risk of d...

Embodiment 1

[0171] Example 1, Comparative analysis of the expression of DKK1 and AFP in non-cancerous liver tissue and hepatocellular carcinoma tissue and corresponding serum

[0172] The present inventors compared and analyzed DKK1 and AFP in 12 cases of non-cancerous liver tissues (4 cases were normal liver tissues, 8 cases were liver cirrhosis tissues) and 16 cases of hepatocellular carcinoma liver tissues (wherein 8 cases of patients had serum AFP≤20ng / ml, and the expression in serum AFP>20ng / ml of the other 8 cases. The results of semi-quantitative reverse transcription polymerase chain reaction (semi-qPCR) and real-time quantitative polymerase chain reaction (qRT-PCR) experiments showed that, compared with AFP, DKK1 was more active in 4 healthy controls (HC) and 8 In cases of liver cirrhosis (liver corrosion, LC), the expression was almost undetectable, but it was highly expressed in most hepatocellular carcinoma tissues (figure 1 A-B, 1D-E).

[0173] Enzyme-linked immunosorbent a...

Embodiment 2

[0175] Example 2. Serum DKK1 is a serum protein marker for the diagnosis of hepatocellular carcinoma

[0176] The inventor according to figure 2 To evaluate the diagnostic ability of serum DKK1 protein in AFP-negative HCC.

[0177] First, the inventors analyzed the expression of serum DKK1 and AFP in each group of the test set. Such as image 3 As shown in A and Table 7, the serum DKK1 protein level of the hepatocellular carcinoma (hepatocellular carcinoma, HCC) group was significantly higher than that of the normal control group (healthy controls, HC), chronic hepatitis B (chronic hepatitis B, CHB) control group and liver In the liver cirrhosis (LC) control group (P image 3 B). The concentrations of serum DKK1 and AFP in each group are shown in Table 8.

[0178] Table 7, the levels of serum DKK1 protein and serum AFP protein in each group in the test set and verification set

[0179]

[0180] Abbreviations: DKK1: dickkopf-1; AFP: alpha-fetoprotein, alpha-fetoprotein;...

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Abstract

The invention discloses an application of DDK1 as a diagnostic marker. Through analysis of a large amount of hepatocellular carcinoma samples, the inventor analyzes the expressions of DKK1 and AFP, firstly discovers that serum DKK1 has a high sensitivity and specificity on diagnosis of hepatocellular carcinoma, especially diagnosis of alpha fetal protein negative hepatocellular carcinoma, identification of hepatocellular carcinoma and alpha fetal protein positive chronic liver disease, and / or diagnosis of hepatocellular carcinoma in the early stage or small hepatocellular carcinoma, and more especially the precision of clinical diagnosis can be largely increased by DKK1-AFP combined diagnosis.

Description

technical field [0001] The present invention belongs to the field of biomedicine; more specifically, the present invention relates to the use of DKK1 as a diagnostic marker, which can be used for: diagnosing alpha-fetoprotein-negative hepatocellular carcinoma, differentiating hepatocellular carcinoma and alpha-fetoprotein-positive chronic liver disease and / or diagnosing Early-stage hepatocellular carcinoma or small hepatocellular carcinoma. Background technique [0002] Primary liver tumors include hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma, cystadenoma of the bile duct, hepatoblastoma, hemangioma, carcinoid, lymphoma, epithelioid vascular endothelium Tumor, squamous cell carcinoma, teratoma, and leiomyosarcoma, fibrosarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma and other liver sarcomas. Hepatocellular carcinoma (HCC) is one of the histological subtypes. Hepatocellular carcinoma (HCC) is one of the most commo...

Claims

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Application Information

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IPC IPC(8): G01N33/574
CPCC12Q1/6886G01N33/57438C07K14/47G01N33/574C12Q2600/158C07K14/4715G01N2333/4703G01N33/57484
Inventor 覃文新沈秋瑾顾健人杨胜利
Owner SHANGHAI INST OF ONCOLOGY
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