CN111458521A - Application of CtBP2 in preparation of diagnosis products for hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma - Google Patents
Application of CtBP2 in preparation of diagnosis products for hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma Download PDFInfo
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- 102100021411 C-terminal-binding protein 2 Human genes 0.000 title claims abstract description 39
- 101710178053 C-terminal-binding protein 2 Proteins 0.000 title claims abstract description 39
- 206010073071 hepatocellular carcinoma Diseases 0.000 title claims abstract description 38
- 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 title claims abstract description 35
- 231100000844 hepatocellular carcinoma Toxicity 0.000 title claims abstract description 32
- 238000003745 diagnosis Methods 0.000 title claims abstract description 11
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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Abstract
The invention discloses an application of CtBP2 as a marker in preparation of diagnosis products of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma, belonging to the technical field of biomedicine. The research result of the invention shows that most of highly-moderately differentiated HCC CtBP2 is negative, and only a few parts of lowly differentiated HCC are positive; in ICC, however, CtBP2 is diffusely strong positive. Therefore, CtBP2 can be used as a marker for preparing related products for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma, and further provides a brand new objective index for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma or evaluating the curative effect of medicaments.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of CtBP2 as a marker in preparation of diagnosis products of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma.
Background
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common pathological types of the two primary liver cancers. HCC often shows hepatocyte differentiation, while ICC shows biliary epithelium differentiation. In addition, there is a relatively rare group of primary liver cancers known as mixed hepatocellular carcinoma-cholangiocarcinoma (CHC), which often shows both hepatocyte and cholangioepithelial differentiation. In most cases, the pathologist can make the correct pathological diagnosis of primary liver cancer by combining clinical presentation, imaging and routine hematoxylin-eosin (H & E) stained sections. However, differential diagnosis of ICC and HCC remains challenging, especially for poorly differentiated tumors.
Immunohistochemistry is often used to aid in the differential diagnosis of HCC and ICC. The most commonly used immunohistochemical markers for the diagnosis of HCC include arginase-1 (ARG1), hepatocyte paraffin-1 (HepPar-1), neutral endopeptidase (CD10), polyclonal carcinoembryonic antigen (pCEA), glypican-3 (GPC3), Bile Salt Efflux Pump (BSEP), and multidrug resistance protein 3(MDR 3). Each marker is reported to have its own drawbacks, including sensitivity and specificity. Cytokeratins CK7 and CK19 are immunohistochemical markers of bile duct epithelial differentiation and can be used as good diagnostic markers of ICC. However, CK7 and/or CK19 have also been reported to have a 10% to 30% positive rate in HCC.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the application of CtBP2 as a marker in the preparation of products for identifying, diagnosing and/or assisting in diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma, and the CtBP2 is used as a diagnostic marker related to hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma to provide an objective index convenient for detection for identification, diagnosis and/or assisting in diagnosis of CtBP2, and has the characteristics of high targeting, stability and sensitivity.
In order to achieve the above object, the present invention adopts the following technical means:
application of CtBP2 as a marker in preparation of products for identifying hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma.
Application of CtBP2 as a marker in preparation of products for diagnosis and/or auxiliary diagnosis of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma.
Further, the product is a diagnostic reagent.
The research results of the invention show that: in non-neoplastic liver tissues, CtBP2 is predominantly expressed on bile duct cells, while hepatocytes are negative; most highly-moderately differentiated HCC CtBP2 are negative, only a few poorly differentiated HCCs are positive; in ICC, however, CtBP2 is expressed as a diffuse strong positive. The above studies suggest that CtBP2 plays an important role in the differential diagnosis of HCC and ICC. Therefore, CtBP2 can be used as a marker for preparing related products for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma, and further provides a brand new objective index for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma or evaluating the curative effect of medicaments.
Drawings
FIG. 1 shows the expression of CtBP2 in non-tumorous liver tissue in example 1.
FIG. 2 shows the expression of CtBP2 in HCC in example 1.
FIG. 3 shows the expression of CtBP2 in ICC in example 1.
Detailed Description
C-terminal binding protein 2(CtBP2) is a transcription accessory repressor and regulator of the CtBP family, playing an important role in regulating physiological and pathological processes. CtBPs inhibit transcription in a histone deacetylase-dependent or independent manner. There is increasing evidence that CtBP2 plays an important role in tumor progression. A recent study showed that CtBP2 can modulate prostate cancer angiogenesis and apoptosis. Overexpression of CtBP2 induces epithelial-to-mesenchymal transition (EMT) of gastric and esophageal squamous cell carcinoma cells and enhances metastatic potential. However, the exact role of CtBP2 in the differential diagnosis of primary liver cancer is still unclear.
The following examples further illustrate the present invention but are not to be construed as limiting the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention. The experimental methods and reagents of the formulations not specified in the examples are in accordance with the conventional conditions in the art.
Example 1
In the embodiment, the accurate function of CtBP2 in differential diagnosis of primary liver cancer is verified by taking healthy people as a control and hepatocellular carcinoma (HCC) and Intrahepatic Cholangiocellular Carcinoma (ICC) patients as research objects.
Liver tissues of healthy persons and patients were fixed in 10% buffered formalin and were paraffin-embedded by routine processing. Immunohistochemical staining was performed on a Dako Omnis fully automated staining instrument following standard procedures.
Antibodies were used as follows: HepPar-1 (Beijing China fir Jinqiao, Cat. No. ZM-0131, dilution 1: 200, clone No. OCH1E5), ARG1 (Zeta, USA, Cat. No. Z2335, dilution 1: 200, clone No. ZM30), CK19 (Beijing China fir Jinqiao, Cat. No. ZM-0074, dilution 1: 800, clone No. UMAB2), CtBP2 (Abcam, Cat. No. ab128871, dilution 1: 300, clone EPR7611[ B ]).
Immunohistochemical staining intensity was divided into 0 (negative), 1+ (weak), 2+ (moderate) and 3+ (strong). Positive cell numbers were scored as focal (< 10%), plaque-like (10% to 50%) or diffuse positive (> 50%). at least 2+ staining of > 10% of cells was positive. Positive was seen in the following staining patterns ① HepPar-1, cytoplasmic granular staining, ② ARG1, cytoplasmic or cytoplasmic/nuclear staining, ③ CK19, cytoplasmic staining, ④ CtBP2, nuclear staining.
In non-neoplastic liver tissues, CtBP2 is predominantly expressed on biliary epithelial cells, while hepatocytes are negative (fig. 1).
Most highly-moderately differentiated HCC CtBP2 were negative, with only 3% (3/100) cases positive; approximately 14.89(14/94) of poorly differentiated HCCs were positive (table 1, figure 2).
TABLE 1194 cases of HCC immunohistochemical staining positives
The positive rate of CtBP2 in both high-medium and low-differentiation ICCs was lower than CK19 (table 1). In ICC, CtBP2 was expressed as a diffuse strong positive (fig. 3), with 100% positive rate in both high-and low-differentiation ICCs (table 2) and higher positive rate in low-differentiation ICC than CK19 (table 2).
TABLE 277 cases of positive staining for ICC immunohistochemistry
From the above results, most of highly-moderately differentiated HCC CtBP2 was negative, and only a few of the lowly differentiated HCCs were positive. In ICC, however, CtBP2 is expressed as a diffuse strong positive. Therefore, CtBP2 can be used for the differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma. Therefore, CtBP2 can be used as a marker for preparing related products for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma, and further provides a brand new objective index for identifying and diagnosing hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma or evaluating the curative effect of medicaments.
Claims (3)
- Application of CtBP2 as a marker in preparation of products for identifying hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma.
- Application of CtBP2 as a marker in preparation of products for diagnosis and/or auxiliary diagnosis of hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma.
- 3. Use according to claim 1 or 2, characterized in that: the product is a diagnostic reagent.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852974A (en) * | 2003-06-09 | 2006-10-25 | 密歇根大学董事会 | Compositions and methods for treating and diagnosing cancer |
| US20160041153A1 (en) * | 2008-11-12 | 2016-02-11 | Kirk Brown | Biomarker compositions and markers |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852974A (en) * | 2003-06-09 | 2006-10-25 | 密歇根大学董事会 | Compositions and methods for treating and diagnosing cancer |
| US20160041153A1 (en) * | 2008-11-12 | 2016-02-11 | Kirk Brown | Biomarker compositions and markers |
Non-Patent Citations (2)
| Title |
|---|
| 张世杰等: "联合应用磷脂酰肌醇蛋白多糖-3(GPC-3)和细胞角蛋白-19(CK-19)免疫组化检测在肝细胞肝癌诊断和鉴别诊断中的价值", 《首都医科大学学报》 * |
| 马娟等: "羧基末端结合蛋白:一种实体肿瘤的致癌因子", 《癌症进展》 * |
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Effective date of registration: 20231211 Address after: Room 301, Building 4, No. 109 Yongfu Road, Tangzha Town Street, Chongchuan District, Nantong City, Jiangsu Province 226000 Patentee after: Jiangsu Suyuan Pathological Diagnosis Center Co.,Ltd. Address before: No.30, Tongyang North Road, Pingchao Town, Tongzhou District, Nantong City, Jiangsu Province, 226361 Patentee before: NANTONG TUMOR Hospital |