Method for predicting prognosis and risk of developing hepatocellular carcinoma in liver cirrhosis patient

A technology for hepatocellular carcinoma and liver cirrhosis, used in measuring devices, instruments, scientific instruments, etc.

Active Publication Date: 2018-07-31
NAT INST OF ADVANCED IND SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, if the serum albumin value is above 3.5, it is judged that there is no decline in the overall liver function, and the prognosis is predicted, but this value may not accurately reflect pa...

Method used

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  • Method for predicting prognosis and risk of developing hepatocellular carcinoma in liver cirrhosis patient
  • Method for predicting prognosis and risk of developing hepatocellular carcinoma in liver cirrhosis patient
  • Method for predicting prognosis and risk of developing hepatocellular carcinoma in liver cirrhosis patient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0266] (Example 1) CSF1R Glycoprotein Analysis Using Immunohistochemical Staining

[0267] Expression studies can be carried out by immunohistochemical staining using lectins or antibodies using specimens (frozen or paraffin-embedded) excised from tissues of patients with various liver diseases, particularly liver cirrhosis or liver cancer. Here, WFA and CSF1R expression in liver cancer tissues were studied using tissue array slides (made from formaldehyde-fixed paraffin-embedded blocks).

[0268] After the tissue array slides were deparaffinized, washed with distilled water, and heated in a microwave oven for 5 minutes in 100 mM citrate buffer (pH 9.0) for antigen activation. Then, endogenous peroxidase inhibition treatment was performed, and blocking buffer (0.2% Tween-20, 5% glycerol, 3% BSA in PBS) was used to block for 20 minutes at room temperature. After washing 3 times in PBS, it was used at 1 μg / mL with primary antibody (anti-CSF1R antibody: C20 clone, Santa Cruz B...

Embodiment 2

[0270] (Example 2) Clinical trial patients with cirrhosis (LC) and without hepatocellular carcinoma (HCC) (LC(+)HCC (-))s Choice

[0271] Serum obtained from 214 patients with type C chronic liver disease who regularly visited Nagoya City University Hospital between January 1998 and January 2013 was used. HBs antigen-positive patients and patients with other organ malignancies within 3 months after enrollment were excluded. The median observation period was 60 months (1 to 195 months), and patients with Child-pugh classification (Child-Pew classification) C were excluded from the study because they could not accurately evaluate the cancer rate and prognosis due to hospital transfer or the like. Liver fibrosis was evaluated by liver biopsy, ultrasound, and CT. Hepatocellular carcinoma is diagnosed by histological examination or imaging based on the criteria of the American Society of Hepatology. The evaluation of fibrosis grade was judged one by one by two pathologists us...

Embodiment 3

[0279] (Example 3) Indicators for predicting the risk of hepatocellular carcinoma in patients with cirrhosis (LC)

[0280] In this example, an index for predicting the risk of developing hepatocellular carcinoma in liver cirrhosis patients (LC) was studied.

[0281] (3-1) WFA in serum of all patients + - CSF1R concentration and WFA + -CSF1R%

[0282] Measurement of WFA using serum samples of all liver disease patients (214) + - CSF1R and total CSF1R concentrations, results are: Serum WFA in cirrhotic patients (LC) (n=115) compared to hepatitis patients (CH) (n=99) + -CSF1R concentration, total CSF1R concentration were significantly higher [WFA + - CSF1R: 208.9 (34.3-500.9) ng / ml vs. 82.3 (5.0-241.0) ng / ml], [total CSF1R: 845.3 (431.6-1487.5) ng / ml vs. 536.4 (266.3-1357.2) ng / ml].

[0283] Among 115 LC patients (59 HCC, 56 non-HCC): Serum WFA + - CSF1R concentration [208.9 (85.4-500.9) ng / ml vs. 213.0 (34.0-442.0) ng / ml] and total CSF1R concentration [820.9 (431.6-1415....

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Abstract

The present invention provides a method and a kit for accurately predicting the prognosis (mortality rate) and risk of developing hepatocellular carcinoma in liver cirrhosis patients. The present invention provides: a method by which an 'index for evaluating the risk of developing hepatocellular carcinoma, 'which is used for predicting the prognosis and risk of developing hepatocellular carcinomain liver cirrhosis patients, is calculated as the ratio of CSF1R that contains WFA/VVA-binding sugars relative to the total CSF1R content of bodily fluid (blood serum) (WFA+-CSF1R%); and a method by which a 'prognosis evaluation index ' is calculated as the amount of CSF1R that contains WFA/VVA-binding sugars (WFA+-CSF1R ng/mL). Furthermore, an optimal cutoff value was determined for each of the indices, and it was proven that: the risk of developing hepatocellular carcinoma was significantly high when the 'index for evaluating the risk of developing hepatocellular carcinoma ' in a subject wasequal to or greater than the optimal cutoff value; and the prognosis was significantly poor when the 'prognosis evaluation index ' was equal to or greater than the optimal cutoff value. In addition,anti-CSF1R antibodies (CSR-1-30), which are exceptional for detecting CSF1Rs such as CSF1Rs that contain WFA/VVA-binding sugars in a bodily fluid sample, were provided. It was discovered that srWFA and VVA lectins other than WFA lectins can be used, and it was additionally proven that measuring the amount of CSF1R that binds to a CSF1R-specific lectin is preferable to measuring the total amount ofCSF1R. It was also possible to provide, inter alia, a kit for measuring the 'prognosis evaluation index ' and/or 'index for evaluating the risk of developing hepatocellular carcinoma ' in a liver cirrhosis patient, the kit including these anti-CSF1R antibodies and lectins as constituent elements.

Description

technical field [0001] The invention of the present application relates to a method and a kit for accurately grasping the progression to hepatocellular carcinoma, evaluating its prognosis, and recurrence after treatment in cirrhosis, which is a severe liver disease. More specifically, there are provided methods and kits for determining the risk of occurrence of hepatocellular carcinoma in cirrhosis and accurately determining the prognosis (survival rate) after treatment, using the method and kit for determining the risk of hepatocellular carcinoma in cirrhosis (F4) and hepatocellular carcinoma The hepatocellular carcinoma sugar chain biomarker highly correlated with the occurrence of liver cirrhosis or the severity of hepatocellular carcinoma is quantified by "hepatocellular carcinoma risk determination index" and / or "cirrhosis prognosis determination index". Background technique [0002] Liver cancer can be broadly classified into primary liver cancer and metastatic liver c...

Claims

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Application Information

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IPC IPC(8): G01N33/574
CPCG01N33/574
Inventor 成松久栂谷内晶雄长诚梶裕之久野敦佐藤隆曾我部万纪千叶靖典池原让田中靖人饭尾悦子
Owner NAT INST OF ADVANCED IND SCI & TECH
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