CN110261612A - The purposes of Aurora-B kinases and Survivin in preparation diagnosis of colorectal carcinoma kit - Google Patents
The purposes of Aurora-B kinases and Survivin in preparation diagnosis of colorectal carcinoma kit Download PDFInfo
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- CN110261612A CN110261612A CN201910542253.4A CN201910542253A CN110261612A CN 110261612 A CN110261612 A CN 110261612A CN 201910542253 A CN201910542253 A CN 201910542253A CN 110261612 A CN110261612 A CN 110261612A
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Abstract
The present invention relates to the purposes of the diagnosing and treating field of colorectal cancer more particularly to aurora-B kinases and survivin in diagnosis colorectal cancer.Present invention solves the problem in that providing a kind of purposes of Aurora B and Survivin in preparation diagnosis of colorectal carcinoma kit.The expression of core Aurora B and cytoplasm Survivin takes part in the lymphatic metastasis of colon cancer, and core Aurora B and cytoplasm Survivin are closely related with the lymphatic metastasis of colon cancer.Core Aurora B and cytoplasm Survivin is the diagnosis marker and therapy target of colorectal cancer.
Description
Technical field
The present invention relates to the diagnosing and treating fields of colorectal cancer more particularly to aurora-B kinases and survivin to tie in diagnosis
Purposes in the carcinoma of the rectum.
Background technique
Aurora-B kinases (i.e. Aurora-B kinases, also known as Aurora B) is serine or Serineprotein kinase family
A member, a variety of substrate proteins of its phosphorylation, to adjust fissional many aspects, from chromatin condensation to cell division.It
It is also a kind of protein of chromosomal passenger complex (CPC), is positioned at from early period to the mid-term later period on transitional centromere,
Cell division is adjusted together with Survivin (Survivin), interior centromere protein (INCENP) and Borealin.Aurora B
Be overexpressed in the kinds cancers such as thyroid cancer, prostate cancer, carcinoma of endometrium, up-regulation with cell Proliferation, prognosis, transfer and
Chromosome number is unstable related, to generate multicore.Before this, it was found that the expression of core Aurora B and carcinoma of mouth
Cell Proliferation, multicore and transfer are related.However, expression of the Aurora B in colorectal carcinoma tissues is still uncertain.
Survivin (Survivin) is a kind of 142 amino acid proteins, inhibits the repetition egg of Apoptosis containing baculoviral
White domain participates in inhibiting Apoptosis.Survivin has an overexpression in a variety of human tumors, but there is no at present about
The research that Survivin and Aurora B are co-expressed in colorectal cancer.
Summary of the invention
The present invention is directed to inquire into the correlation of Aurora B and Survivin expression and correlated pathologies.The present invention solves
The problem of be to provide a kind of purposes of Aurora B and Survivin in preparation diagnosis of colorectal carcinoma kit.
In colorectal cancer patients, while detecting the expression of Aurora B and Survivin, wherein Aurora B and
High expression of the Survivin in subject's colon epithelial cell has shorter Overall survival than low expression.
Aurora B and Survivin expression can be the detection carried out in protein level, be to pass through immuning tissue
Chemical staining measurement.
It will be understood by those skilled in the art that the diagnostic kit can be any conventional form in this field, examination
Reagent used in agent box can be different with kit type, and kit includes more grams of Aurora B and Survivin
Grand antibody or monoclonal antibody and other conventional reagents.
The expression of core Aurora B and cytoplasm Survivin takes part in the lymphatic metastasis of colon cancer, core Aurora B and
Cytoplasm Survivin is closely related with the lymphatic metastasis of colon cancer.Core Aurora B and cytoplasm Survivin is colorectal cancer
Diagnosis marker and therapy target.
Detailed description of the invention
Fig. 1 is immunohistochemical staining；
In normal colonic mucosa cell AuroraB (a) and Survivin (c) dyeing it is weaker, nucleus Aurora B (b) and
Caryoplasm Survivin (d) expression is dyed relatively strong in colorectal cancer.
Fig. 2 is the core Aurora B and caryoplasm Survivin for having low expression (0%) in normal colonic mucosa, 58.5%
Case is Aurora B nuclear staining, and 73.8% case is the nuclear staining of Survivin, and 41.5% case is Survivin's
Cytoplasm dyeing.
Fig. 3 is that immunohistochemistry detects table of the Aurora B and Survivin in colorectal carcinoma or metastatic lymph node
It reaches；
Low core AuroraB expression (N-) (a) He Gaohe AuroraB expression (N+) (b and c), low core Survivin expression and
Cytoplasm Survivin high express (N-C+) (d), high core Survivin expression and low cytoplasm Survivin expression (N+C-) (e) and
High core and cytoplasm Survivin expression (N+C+) (f) are primary colorectal carcinoma cancer typical example, and high core Aurora B expresses (N+) (g)
It is metastatic lymph node typical example with low core Survivin expression and high cytoplasm Survivin expression (N-C+) (h).
Specific embodiment
Below with reference to specific embodiment, the present invention is described in further detail, it is described be explanation of the invention and
It is not to limit.
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material and reagent as used in the following examples, are commercially available unless otherwise specified.
Embodiment 1
Material and method
Patient: 65 trouble for receiving advanced colorectal cancer operation excision in Hiroshima,Japan memorial hospital are included in this research altogether
Person.In addition, 20 normal colonic mucosas are as control.The tumour progress formalin of each patient is fixed and is cut into parallel
4-5mm slice, is dyed in conjunction with h and E, selects the most deep infringement position of tumour by microexamination.This is studied
To the approval of Hiroshima Ethics Committee, memorial hospital.All subjects obtain informed consent.
Immunohistochemical staining.Immunohistochemistry is carried out to Aurora B and Survivin with LSAB system (kyoto, Japan reaches section)
Dyeing.In short, paraffin mass is cut into 3-4 μm of slice.It will be sliced the 2h that dewaxes in dimethylbenzene, with classification ethyl alcohol washing
(100-70%) dehydration, with 3% hydrogen peroxide treatment 30 minutes.It will slice steam pressure 3 in 10mM citrate buffer solution (pH6.0)
Secondary 5 minutes, to repair antigen, by anti-Aurora B primary monoclonal antibody (California, USA Santiago conduction experiments room；1:50
Dilution).San Diego, CA, USA city, 1:50 dilution) and anti-Survivin polyclonal antibody (NB500-201,
This biotech firm of Nova, Littleton, the U.S.；1:1000 dilution) overnight incubation in 4 DEG C.It is fixed by nuclear location and cytoplasm
The expression of Aurora B and Survivin are estimated in position, sxemiquantitative.Immunoreactivity is classified by the percentage of positive tumor cell, point
Not are as follows: +++, strong (> 60% tumour cell contaminates by force)；++, in (20-60% contaminates by force)；+, it is light (< the last 20% dye or weak dye)；Or-
It does not dye.Survivin and AuroraB positive case is divided into ++ or +++ grade, negative case is divided into-or+grade.
Statistically analyze Regional Lymph Nodes of Colorectal Cancer transfer, lymph infringement, vein infringement, the pathological factors such as DISTANT METASTASES IN and
The relationship of AuroraB and Survivin expression.Use χ2Or precise probabilistic method compares the data between two groups.P < 0.05 is considered as
Statistical significant difference.
As a result
The expression of AuroraB and Survivin in normal colonic mucosa and Colorectal Carcinoma.Use immunohistochemical method
Have detected the expression of Aurora B and Survivin in 20 normal colonic mucosas and 65 Colorectal Carcinomas.It is viscous in Normal Colon
Extremely weak AuroraB and Survivin dyeing (a and c and table 1 in Fig. 1) are shown in theca cell.Core Aurora B and core
And/or cytoplasm Survivin shows to dye (b and d and table 1 in Fig. 1) by force in colorectal cancer.All cases are shown just
Low core Aurora B expression, low core and cytoplasm Survivin in normal colonic mucosa.There are 38 (58.5%) tables in 65 patients
Now it is Aurora B nuclear staining, there are 48 (73.8%) to show as survivin nuclear staining in 65 patients, have in 65 patients
27 (41.5%) show as cytoplasm dyeing (Fig. 2, Fig. 3 and table 1).
The expression of Aurora B and Survivin in 1 normal colonic mucosa of table and Colorectal Carcinoma
The correlation research of Aurora B and Survivin expression and colorectal cancer pathological factor.We have detected pathology because
The correlation of expression of the element with AuroraB and/or Survivin in colorectal cancer.Compared with core negative patient, Aurora
B core positive patient lymphatic metastasis obviously increases (P < 0.01).Survivin cytoplasm positive case and Survivin cytoplasm
Negative case is compared, and lymphatic metastasis obviously increases (P < 0.01), and Survivin core positive case is poor compared with negative case
It is different not significant.Core Aurora B and cytoplasm Survivin expression is (table 2) an important factor for influencing prognosis mala.
The correlation research of 2 Aurora B of table, Survivin expression and colorectal cancer pathological factor
Inquire into the relationship of core Aurora B and colorectal cancer cells cytoplasm Survivin expression and pathological factor.Cytoplasm
Survivin is positive, core Aurora B positive expression is significant related (P < 0.001, P < 0.05) to lymphatic metastasis, with positive born of the same parents
Matter Survivin and feminine gender core Aurora B expression, feminine gender cytoplasm Survivin and feminine gender core AuroraB expression (table 3),
Core AuroraB and cytoplasm Survivin shows 76% lymphatic metastasis.
The expression and the correlation of cytoplasm Survivin and pathological factor of 3 core Aurora B of table
Expression and pathological factor of the Aurora B and Survivin in primary colorectal tumour and lymphatic metastasis.It grinds
The expression variation of AuroraB and Survivin in primary colorectal tumour and lymphatic metastasis is studied carefully.
Metastatic tumor patient is compared with primary tumo(u)r, and core Aurora B and cytoplasm Survivin expression frequency are higher, core
Survivin expression frequency is lower (g and h, table 4 in Fig. 3).
4 AuroraB/Survivin of table expression and primary tumor/metastatic lymph node relationship
This research has detected Aurora in 20 normal colonic mucosas and 65 Colorectal Carcinomas using ImmunohistochemistryMethods Methods
The expression of B and Survivin.The result shows that: there are the high tables of core Aurora B, core and cytoplasm Survivin in colorectal cancer cells
It is expressed up to frequent.In addition, the overexpression of core Aurora B and cytoplasm Survivin are significant related to lymphatic metastasis.
Aurora B kinases is a kind of chromosome passenger albumen, and dye is realized by the phosphorylation of mitosis histone H 3
Colour solid separation.The phosphorylation state of histone H 3 can be balanced by Aurora B kinase activity and PPI phosphatase activity.
The overexpression of Aurora B generates multicore and increases ploidy, this is important in the development process of human cancer.At this
In item research, we have detected expression of the Aurora B in colorectal cancer.The expression of Aurora B is bright in Colorectal Carcinoma
Aobvious to be higher than normal colonic mucosa tissue, the high expression of core Aurora B is related with lymphatic metastasis.We are previously found core
The expression of Aurora B is proliferated with cancer cell of oral cavity, multicore and transfer are related.The expression of Aurora B also with prostate cancer (4
Example), carcinoma of endometrium (3) it is related with thyroid cancer (5) prognosis mala.Aurora B is also responsible for the thin of carcinogenic ras mediation
Dysuria with lower abdominal colic causes tumour cell to accelerate proliferation.Therefore, the result of these reports confirms the result of this research.Aurora B mistake
Expression promotes the specific mechanism of transfer to wait to illustrate.Therefore, the overexpression of Aurora B and colorectal cancer cells are migrated or are invaded
Between relation value must study.
Survivin is a kind of inhibition apoptosis and adjusts fissional bifunctional protein.Core Survivin can control carefully
Born of the same parents' division, and cytoplasm Survivin is considered as cytoprotection.Survivin is in BIR structural domain and the end COOH α spiral
Between bonding pad have a nuclear export signal (NES).Certain researchs the result shows that, after being treated with leptomycin B, cell
The accumulation of core transposition and cytoplasm Survivin.In our study, cytoplasm Survivin is related with lymphatic metastasis.Carefully
Cytoplasm Survivin has the characteristics that anti-apoptotic, related with micro-pipe, directly or indirectly interferes the function of caspase.We
As a result the support also observed, the i.e. cytoplasmic expression of Survivin and breast cancer (17), lymthoma (18), liver cancer
(19) are related to the poor prognosis of gastric cancer (20).In research in our prior, the excessive table of cytoplasm Survivin is found
Up to related with colorectal cancer prognosis mala).
It is previous studies have shown that a subunit of the survivin as chromosomal passenger complex (CPC), and with CPC's
Other subunits (such as aurorab, incenp and borealin) interaction, to adjust cell division.It was found that in oral cavity
In squamous carcinoma (OSCC), the expression of core Survivin is significant related to the expression of Ki-67 and AuroraB.It is worth noting that, there is core
The OSCC patient of Survivin and Aurora B expression shows apparent malignant activity.However, in our current research, core
Survivin is unrelated with the Aurora B and pathological factor of colorectal cancer.Compared with OSCC, the expression of survivin in colorectal cancer
Frequency is very high, thus core survivin may play the role of in epithelioma and gland cancer it is different.
During this investigation it turned out, we have found that the overexpression of core Aurora B and cytoplasm Survivin it is significant it is related with
Lymphatic metastasis.In addition, core AuroraB and cytoplasm survival rate show that colorectal cancer prognosis is very different.Therefore, core Aurora
B and cytoplasm Survivin may be the important symbol for predicting colorectal cancer grade malignancy.
In conclusion our result of study shows that the expression participation of core Aurora B and cytoplasm Survivin finishes
The lymphatic metastasis of intestinal cancer, core Aurora B and cytoplasm Survivin are closely related with the lymphatic metastasis of colon cancer.
It is therefore believed that core Aurora B and cytoplasm Survivin are the diagnosis marker and therapeutic target of colorectal cancer
Point.
Claims (3)
- Purposes of the 1.Aurora B and Survivin in preparation diagnosis of colorectal carcinoma kit.
- 2. purposes according to claim 1, which is characterized in that the Aurora B and Survivin expression are to pass through Immunohistochemical dyeing measurement.
- 3. purposes according to claim 2, which is characterized in that the diagnosis of colorectal carcinoma kit include Aurora B and The polyclonal antibody or monoclonal antibody of Survivin.
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| WO2022253604A1 (en) | 2021-06-03 | 2022-12-08 | Metacurum Biotech Ab | Biomarkers and uses thereof |
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| WO2022253604A1 (en) | 2021-06-03 | 2022-12-08 | Metacurum Biotech Ab | Biomarkers and uses thereof |
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Application publication date: 20190920 |