CN111190007B - Application of CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis - Google Patents
Application of CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis Download PDFInfo
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- CN111190007B CN111190007B CN202010014505.9A CN202010014505A CN111190007B CN 111190007 B CN111190007 B CN 111190007B CN 202010014505 A CN202010014505 A CN 202010014505A CN 111190007 B CN111190007 B CN 111190007B
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- breast cancer
- ccdc25
- membrane protein
- metastasis
- prognosis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Abstract
The invention discloses an application of a membrane protein CCDC25 in predicting breast cancer prognosis or inhibiting breast cancer distant organ metastasis and a kit, wherein the kit comprises a reagent for detecting the expression quantity of the membrane protein CCDC25 in a breast cancer patient; in addition, neutralizing antibodies against the membrane protein CCDC25 inhibit metastasis of breast cancer cells. The kit of the invention assists the existing prognosis diagnosis to improve the survival rate of patients; the invention also provides a novel breast cancer treatment scheme.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis.
Background
According to the research data of CA2018, 209 ten thousand of the 1810 new malignant tumor patients are predicted to be breast cancer patients in 2018, which account for 1/4 of the total number of new malignant tumor of women, and 63 thousand of the patients die of breast cancer, which is the most death of all female malignant tumors. In breast cancer patient deaths, distant metastasis of the tumor is the leading cause of breast cancer deaths. Therefore, predicting the prognosis of breast cancer patients and inhibiting the distant metastasis of tumors as early as possible are the keys for improving the survival curative effect of the patients.
The current treatment for patients with advanced breast cancer mainly comprises radiotherapy, chemotherapy, endocrine therapy and targeted therapy, and although the comprehensive treatment scheme effectively improves the prognosis of breast cancer patients, part of the patients still have difficulty in escaping metastasis and recurrence. In the face of the current situation, a better prognosis prediction method is not available temporarily, and a treatment means directly aiming at a breast cancer metastasis mechanism is not available.
The treatment of advanced breast cancer mainly depends on a comprehensive treatment scheme combining radiotherapy, chemotherapy, endocrine therapy and targeted therapy, and the prognosis of a patient is improved to a certain extent. However, even if a plurality of treatment means are combined, the problem of relapse and metastasis still remains to be very troublesome, and the reason for the relapse and metastasis is that the research on the biological behavior of malignant tumors is insufficient in the past and the treatment means directly aiming at the tumor metastasis mechanism is further lacked. Only by deeply understanding the complex biological behavior of tumor metastasis can a new idea be provided for the diagnosis and treatment of breast cancer.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides the application of the membrane protein CCDC25 in preparing a kit for the prognosis diagnosis of breast cancer and a cancer suppressor drug, wherein the kit comprises a reagent for detecting the expression quantity of the membrane protein CCDC25, and the kit can assist the existing prognosis diagnosis so as to improve the survival rate of a patient; in addition, inhibitory monoclonal antibodies of the membrane protein CCDC25 can inhibit metastasis of breast cancer cells.
In order to achieve the purpose, the invention adopts the technical scheme that: a kit for breast cancer prognosis diagnosis comprises a reagent for detecting the expression level of the membrane protein CCDC 25.
As an improvement of the technical scheme, the reagent comprises a membrane protein CCDC25 antibody.
The invention also provides a medicament for inhibiting breast cancer metastasis, which comprises a membrane protein CCDC25 neutralizing antibody.
As an improvement of the technical scheme, the membrane protein CCDC25 inhibitor is a membrane protein CCDC25 inhibitory monoclonal antibody.
As an improvement of the technical scheme, the composition also comprises pharmaceutically acceptable auxiliary materials.
In addition, the invention also provides a detection method of the kit, which comprises the following steps:
(1) preparing primary focus tissues of a breast cancer patient into tissue slices;
(2) dewaxing, hydrating, antigen retrieval and incubating CCDC25 monoclonal antibodies on the slices in the step (1);
(3) detecting the slices in the step (2) by adopting a DAB color development method;
(4) recording the expression level of CCDC25 of the tumor cells; the relevant data was analyzed by SPSS software.
The invention has the beneficial effects that: the invention provides application of a membrane protein CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis and a kit. The kit is mainly used for detecting the membrane protein CCDC25 in the distant organ metastasis of the breast cancer cells of a breast cancer patient, the expression level of CCDC25 has strong correlation with the prognosis of the breast cancer patient, and the expression level of CCDC25 can be used as the index of the prognosis of the breast cancer patient; the kit has the following advantages: 1) is suitable for all breast cancer patients; 2) the detection is convenient, the detection index is obviously related to the prognosis, the detection index is single, and the operation is simple; 3) all reagents are mostly common, and the cost is controlled within a feasible range. In addition, the present invention provides a new breast cancer treatment regimen: the CCDC25 inhibitor can inhibit the metastasis of breast cancer cells.
Drawings
FIG. 1 shows the relationship between the level of CCDC25 expression in breast cancer tissues and the prognosis of breast cancer, wherein the ordinate represents the survival rate of liver metastasis; the upper curve samples were from breast cancer patients with lower levels of CCDC25 expression; the samples of the lower curve are from breast cancer patients with higher expression level of CCDC 25; the numbers following the parenthesis indicate the number of samples.
Fig. 2 shows that liver metastasis decreased following tumor cell knockdown of CCDC25, with arrows representing liver metastasis foci.
Detailed Description
In order to more concisely and clearly demonstrate technical solutions, objects and advantages of the present invention, the following detailed description of the present invention is provided with reference to specific embodiments and accompanying drawings.
Example 1: correlation of expression of CCDC25 in tumor cells with prognosis of breast cancer patients
Collecting primary focus tissues of breast cancer patients in hospitals, and preparing tissue slices through fixing, dehydrating, embedding, slicing and the like; dewaxing, hydrating, repairing antigen, sealing and the like are carried out on the pathological section, and the CCDC25 monoclonal antibody is incubated with the tissue section; detecting the tissue slices by using a DAB color development method; and recording the expression change of the tumor cells CCDC 25. The results are shown in fig. 1, and by analyzing the expression of CCDC25 and survival of liver metastasis of breast cancer in breast cancer tissues, the expression level of CCDC25 is found to be obviously related to prognosis: the lower the expression of CCDC25, the higher the survival rate of breast cancer liver metastasis patients; the higher the expression of CCDC25, the lower the survival rate of patients with liver metastases of breast cancer.
Example 2: the tumor cell knocking-down CCDC25 can obviously inhibit the liver metastasis of the tumor.
Construction of tumor cells knocking down CCDC25 expression: the breast cancer MDA-MB-231 cell strain is respectively infected with shRNA virus containing CCDC25 and negative control shluc virus, and after 48 hours of infection, 2.5ug/ml puromycin is used for screening for 2 weeks to obtain a stable cell strain. The normal MDA-MB-231 cell line and the MDA-MB-231 cell line with the knocked-down CCDC25 are mixed at the ratio of 1X 106The amount of 50ul was injected into the spleen of a mouse, and 30 days later, the mouse was placed under PET-CT to observe the liver metastasis of tumor cells. The results are shown in fig. 2, the blank control group (UT) and the negative control group (shluc) can obviously have liver metastasis foci in the liver part of the mice, which indicates that liver metastasis occurs; and experimental group (sh CCDC 25)1、sh CCDC252) No liver metastasis was found. This suggests that CCDC25 can be used as a target for breast cell metastasis, and the liver metastasis of breast cancer can be effectively inhibited by blocking CCDC25 expression with inhibitory CCDC25 monoclonal antibody.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (6)
1. Application of membrane protein CCDC25 in preparing a kit for predicting breast cancer prognosis or a medicament for inhibiting breast cancer distant organ metastasis.
2. The use according to claim 1, wherein the kit comprises a reagent for detecting the expression level of the membrane protein CCDC 25.
3. The use of claim 2, wherein the agent comprises the membrane protein CCDC25 antibody.
4. The use of claim 1, wherein the medicament comprises a membrane protein CCDC25 neutralizing antibody.
5. The use of claim 4, wherein the membrane protein CCDC25 neutralizing antibody is membrane protein CCDC25 inhibitory mAb.
6. The use of claim 5, wherein the medicament further comprises a pharmaceutically acceptable excipient.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010014505.9A CN111190007B (en) | 2020-01-07 | 2020-01-07 | Application of CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis |
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| CN202010014505.9A CN111190007B (en) | 2020-01-07 | 2020-01-07 | Application of CCDC25 in predicting breast cancer prognosis and inhibiting breast cancer distant organ metastasis |
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| CN111190007A CN111190007A (en) | 2020-05-22 |
| CN111190007B true CN111190007B (en) | 2022-02-25 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2687609A2 (en) * | 2008-11-10 | 2014-01-22 | The United States of America As Represented by the Secretary Department of Health and Human Services | Method for treating solid tumor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2687609A2 (en) * | 2008-11-10 | 2014-01-22 | The United States of America As Represented by the Secretary Department of Health and Human Services | Method for treating solid tumor |
Non-Patent Citations (1)
| Title |
|---|
| High expression of CCDC25 in cholangiocarcinoma tissue samples;SIRIPORN PROUNGVITAYA等;《SIRIPORN PROUNGVITAYA》;20171231;第14卷;摘要 * |
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Effective date of registration: 20220402 Address after: 510000 room 751, room 406, No. 1, Yichuang street, Huangpu District, Guangzhou City, Guangdong Province (Zhongxin Guangzhou Knowledge City) Patentee after: Songbo (Guangzhou) biomedical Co.,Ltd. Address before: Sun Yat Sen Memorial Hospital, Sun Yat sen University, 107 Yanjiang West Road, Guangzhou, Guangdong 510030 Patentee before: SUN YAT-SEN MEMORIAL HOSPITAL, SUN YAT-SEN University |