CN103235141A - Application of ATF (activating transcription factor) 3 to predicting bladder cancer metastasis and judging prognosis - Google Patents
Application of ATF (activating transcription factor) 3 to predicting bladder cancer metastasis and judging prognosis Download PDFInfo
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- CN103235141A CN103235141A CN2013101518390A CN201310151839A CN103235141A CN 103235141 A CN103235141 A CN 103235141A CN 2013101518390 A CN2013101518390 A CN 2013101518390A CN 201310151839 A CN201310151839 A CN 201310151839A CN 103235141 A CN103235141 A CN 103235141A
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Abstract
The invention relates to application of an ATF (activating transcription factor) 3 protein to preparation of a kit for detecting or judging bladder cancer metastasis and judging bladder cancer prognosis. The invention also provides the kit for detecting or judging bladder cancer metastasis and judging bladder cancer prognosis. The invention has the following advantages: the invention provides a new protein marker for predicting bladder cancer metastasis of patients with bladder cancers and judging prognosis and the protein marker can be used for detecting or judging bladder cancer invasion and metastasis degrees and judging prognosis by an immunohistochemical detection method; the invention provides the new kit for predicting bladder cancer metastasis of the patients with bladder cancers and judging prognosis; and the invention provides the new application of the ATF 3 protein to suppressing bladder cancer metastasis and lengthening the prognostic lifetime of the patients with bladder cancers.
Description
Technical field
The present invention relates to oncology and diagnostic field, specifically, is that ATF3 is used to predict that carcinoma of urinary bladder shifts and the application of judging prognosis.
Background technology
Carcinoma of urinary bladder is human Genitourinary common malignancy (Siegel et al., 2013), and in China, the carcinoma of urinary bladder incidence of disease has the trend of increasing, and occupies the first place of male genitourinary system tumour.Invasion and attack and transfer are to cause the failure of tumor of bladder patient treatment and dead main reason.But at present carcinoma of urinary bladder shifts that cutter system is not clear and definite as yet really, lacks the protein marker of judging that carcinoma of urinary bladder shifts clinically.
Activating transcription factor 3(ATF3) be a stress reaction induced gene, this gene is positioned at chromosome lq32.3, and 181 the amino acid whose DNA that encode are in conjunction with albumen (Liang et al., 1996).The ATF3 gene contains 4 extron A, B, C, E, is the transcription factor of leucine zipper contained structure.ATF3 participates in the stress reaction that cell adapted internal and external environment changes.ATF3 can be according to target gene and cellular environment different, activate or the inhibition related gene expression, has transcriptional regulation widely, participate in also simultaneously that the body stable state is kept, physiology and pathologic process (Thompson et al., 2009) such as wound healing, cell adhesion, apoptosis and signal conduction.
ATF3 also has vital role in the generation of tumour development and invasion and attack transfer process.ATF3 may bring into play difference even opposite effect under different cell types or homocellular different conditions.It both can be used as oncogene, also can be used as tumor suppressor gene and played a role.Have and studies show that in tumour cells such as breast cancer, prostate cancer, dermoid cancer, the high expressed of ATF3 can promote growth and invasion and attack (Yin et al., 2008 of tumour cell; Yin et al., 2010).Express and ATF3 is low in tumour cells such as cervical carcinoma and colon cancer, induce it to cross in the growth that can suppress tumour cell after the expression and the body and become knurl ability (Hackl et al., 2010).Expression and the functional study of ATF3 in carcinoma of urinary bladder is still unknown.
Diagnosis of bladder cancer mainly relies on inspection methods such as cystoscope, urine at present, yet these detection methods all have certain limitation.For example because of the limited higher false negative rate that has of drawing materials, and can't judge transfer case and the prognosis situation of tumour.Seek the emphasis that the detection method of effectively judging the orders of severity such as cancer metastasis is research always.Yet, at present existingly still lack gratifying protein marker at cancer detection, more lack the mark that can be used for detecting or judging the carcinoma of urinary bladder transfer case.
Therefore, this area presses for the relative differential protein mark that exploitation can be used for detecting or judging carcinoma of urinary bladder transfer and judging prognosis.
Summary of the invention
The objective of the invention is at deficiency of the prior art, provide ATF3 albumen for the preparation of the application that detects or judge in the kit that carcinoma of urinary bladder shifts.
Purpose of the present invention second is that the application of ATF3 albumen in the kit of judging for the preparation of the carcinoma of urinary bladder prognosis is provided.
Purpose of the present invention the 3rd is, provide a kind of for detection of or judge the kit that carcinoma of urinary bladder shifts.
Purpose of the present invention the 4th is that a kind of kit for carcinoma of urinary bladder prognosis judgement is provided.
Purpose of the present invention the 5th is that the application of a kind of ATF3 albumen in the medicine that preparation inhibition carcinoma of urinary bladder shifts is provided.
Sextus purpose of the present invention is, provides a kind of ATF3 albumen to improve application in the medicine of prognosis life cycle of bladder cancer patients in preparation.
For realizing above-mentioned first purpose, the technical scheme that the present invention takes is: ATF3 albumen is for the preparation of the application that detects or judge in the kit that carcinoma of urinary bladder shifts.
Described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen, and the profit metastasis degree of invading of the expression of described ATF3 albumen and carcinoma of urinary bladder is negative correlation.
For realizing above-mentioned second purpose, the technical scheme that the present invention takes is: the application of ATF3 albumen in the kit of judging for the preparation of the carcinoma of urinary bladder prognosis.
Described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen, and the prognosis of the expression of described ATF3 albumen and bladder cancer patients is proportionate life cycle.
For realizing above-mentioned the 3rd purpose, the technical scheme that the present invention takes is: a kind of for detection of or judge the kit that carcinoma of urinary bladder shifts, described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen.
The profit metastasis degree of invading of the expression of described ATF3 albumen and carcinoma of urinary bladder is negative correlation.
For realizing above-mentioned the 4th purpose, the technical scheme that the present invention takes is: a kind of kit for carcinoma of urinary bladder prognosis judgement, described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen.
The prognosis of the expression of described ATF3 albumen and bladder cancer patients is proportionate life cycle.
For realizing above-mentioned the 5th purpose, the technical scheme that the present invention takes is: the application of ATF3 albumen in the medicine that preparation inhibition carcinoma of urinary bladder shifts.
For realizing above-mentioned the 6th purpose, the technical scheme that the present invention takes is: ATF3 albumen improves application in the medicine of prognosis life cycle of bladder cancer patients in preparation.
The invention has the advantages that:
1. the prediction bladder cancer patients shifts and the protein marker of judging prognosis to the invention provides a kind of new being used for, and by method for immunohistochemical detection, can be used for detecting or judging carcinoma of urinary bladder invasion and attack and metastasis degree and judging prognosis;
2, the prediction bladder cancer patients shifts and the kit of judging prognosis to provide a kind of new being used for;
3, the new purposes that carcinoma of urinary bladder shifted and improved prognosis life cycle of bladder cancer patients that be used for to suppress of ATF3 albumen is provided.
Description of drawings
Fig. 1 has shown ATF3 at the relative high expressed with the mucomembranous surface cell of normal bladder basic unit, and Bladder Cancer is low relatively express (A) of holostrome, and statistics shows that the expression intensity of progressive stage carcinoma of urinary bladder is lower than carcinoma in situ and optimum bladder disease (B).
Fig. 2 shows that WB confirms in the same case that ATF3 albumen and gene expression dose all significantly are lower than cancer beside organism (A) in the Bladder Cancer.Real-time PCR result also confirms ATF3 low relatively express (B) in Bladder Cancer.
Fig. 3 shows the lower or loss of expression of clinical carcinoma of urinary bladder case ATF3 expression of invading profit degree height (invade the profit holostrome or DISTANT METASTASES IN takes place), express higherly relatively and do not invade profit transfer bladder cancer (being limited to the top layer) ATF3, ATF3 strengthens with the invasion and attack degree of carcinoma of urinary bladder and is low expression (A).Statistics demonstration ATF3 expresses and invades the profit metastasis degree and is negative correlation (B).
Fig. 4 utilizes the bladder cancer cell line of different metastatic potentials to carry out functional study, and behind the reticent expression ATF3, scratch experiment shows the healing time (A) that can obviously accelerate transitional cell bladder carcinoma cell line in low metastatic bladder cancer cell line (T24).The reticent expression of Transwell invasion and attack experiment confirm ATF3 can strengthen the transfer ability (B) of transitional cell bladder carcinoma cell line.The animal metastasis model further confirms in the body, and after reduction ATF3 expressed, transitional cell bladder carcinoma cell line lung metastasis rate and metastatic nodules all significantly increased (C).
The carcinoma of urinary bladder case of the low expression of Fig. 5 patient's survivorship curve demonstration ATF3 shortens life cycle relatively.
Embodiment
Below in conjunction with accompanying drawing embodiment provided by the invention is elaborated.
1. sample: the fresh resection organization of clinical bladder cancer patients sample
2. antibody: Anti-ATF3 antibody (HPA001562), the anti-people's polyclonal antibody of rabbit is available from the Sigma Aldrich(U.S.).
3. SABC method:
The tissue samples of the fresh excision of clinical bladder cancer patients prepares paraffin section, and paraffin section dewaxes to water through dimethylbenzene and gradient alcohol, the PBS washing.Every section adds 50 μ l, 0.3% H
2O
2, the blocking-up endogenous peroxidase activity.The section put into antigen retrieval liquid (Tris-EDTA, pH9.0), microwave 30 min.The section balance adds 50 μ l sealing serum to the room temperature, inhales behind 10 min and removes unnecessary serum, adds the anti-people ATF3 of 50 μ l rabbits antibody again, or PBS replaces primary antibodie to get rid of false positive, and 4 oC spend the night, and to add biotin labeled anti-rabbit two anti-in the back, room temperature 10 min.PBS washing back adds 50 μ l streptavidin peroxidase solution, room temperature 10 min.The DAB colour developing, microscopically is observed 3～10 min.The tap water flushing, haematoxylin is redyed, hydrochloride alcohol differentiation, neutral gum mounting.The connective tissue section adjacent with carcinoma of urinary bladder is used for carrying out haematoxylin-Yihong (HE) dyeing.
4. the SABC result judges and grade scale
Immunohistochemical observation result adopts double-blind study.As positive control, every group all replaces primary antibodie to make negative control with PBS with known positive sheet.Positive cell percentage and staining power carry out comprehensive grading in the sample, and positive cell percentage is 5 high power lenses (10 * 40) positive cell percentages in the visual field at random: tinctorial strength is kept the score with the dyeing situation of most cells, marks with sxemiquantitative.Painted tenuigenin and the nucleus of being positioned of ATF3 protein positive is pale brown look or sepia.Give a mark by staining power earlier: 0 be divided into colourless, 1 be divided into a little less than (light yellow), 2 be divided in (pale brown look), 3 are divided into (sepia) by force.Press positive cell percentage (%) marking again: 0 minute is negative, and 1 is divided into positive cell≤10%, 2 is divided into positive cell 11%～50%, and 3 are divided into positive cell 51%～80%, and 4 are divided into positive cell〉80%(sees Table 1).At last by hundred parts of positive cells in the sample when staining power carry out comprehensive grading, every section is observed 5 discontinuous high power fields respectively in the middle of reaching up and down, average is the integrated value of this section.The product that every routine final score is staining power and positive cell percentage (A * B): 0 is divided into (-), and 1～4 is divided into the weak positive (+), and 5～8 minutes positive (++), 9～12 are divided into strong positive (+++).Result's judgement is carried out under double blinding, and every section is counted respectively by two high age and service seniority doctors of pathology department.
Table 1. SABC is judged grade scale
5. statistical analysis
Use Graphpad Prism software development data statistic analysis.Each group data is at first carried out test of normality, and the normal distribution data represent that with Mean ± SD the difference of each variable is checked with one-parameter variance analysis and t between group.
P＜0.05 is significance limit.
6. conclusion
Please refer to accompanying drawing 1-5, the present invention finds first that through extensive and deep research ATF3 is a kind of new carcinoma of urinary bladder nm-23.ATF3 in the normal bladder epithelial cell high expressed and in Bladder Cancer downward modulation express, be negative correlation with the profit metastasis degree of invading of carcinoma of urinary bladder.The vivo and vitro functional study shows the expression of ATF3 to the influence of transitional cell bladder carcinoma cell line propagation nothing, but can obviously suppress the transfer of carcinoma of urinary bladder.Showing that ATF3 albumen can be used as suppresses the medicine that carcinoma of urinary bladder shifts prognosis life cycle of improving bladder cancer patients.In addition, patient's survivorship curve shows that the case of low expression ATF3 obviously shortens life cycle.Therefore, the low expression of ATF3 can be used as the judgement symbol thing that detects carcinoma of urinary bladder transfer and carcinoma of urinary bladder prognosis.
A kind of for detection of or judge that the kit that carcinoma of urinary bladder shifts, described kit are the excision tissue sections that detects bladder cancer patients by immunohistochemistry technique, the expression of detection ATF3 albumen.Detection method is with reference to embodiment 1.The profit metastasis degree of invading of the expression of described ATF3 albumen and carcinoma of urinary bladder is negative correlation.That is, the bladder cancer patients metastatic potential of low expression ATF3 is big.
A kind of kit for carcinoma of urinary bladder prognosis judgement, described kit are the excision tissue sections that detects bladder cancer patients by immunohistochemistry technique, detect the expression of ATF3 albumen.Detection method is with reference to embodiment 1.The prognosis of the expression of described ATF3 albumen and bladder cancer patients is proportionate life cycle.That is, the prognosis of the low expression of ATF3 bladder cancer patients is shorter than the bladder cancer patients of high expressed ATF3 life cycle relatively.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the inventive method; can also make some improvement and replenish, these improvement and replenish and also should be considered as protection scope of the present invention.
Claims (10)
1.ATF3 albumen is for the preparation of the application that detects or judge in the kit that carcinoma of urinary bladder shifts.
2. application according to claim 1, it is characterized in that, described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen, and the profit metastasis degree of invading of the expression of described ATF3 albumen and carcinoma of urinary bladder is negative correlation.
3.ATF3 the application of albumen in the kit of judging for the preparation of the carcinoma of urinary bladder prognosis.
4. application according to claim 3, it is characterized in that, described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen, and the prognosis of the expression of described ATF3 albumen and bladder cancer patients is proportionate life cycle.
One kind for detection of or judge the kit that carcinoma of urinary bladder shifts, it is characterized in that described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, the expression of detection ATF3 albumen.
6. kit according to claim 5 is characterized in that, the profit metastasis degree of invading of the expression of described ATF3 albumen and carcinoma of urinary bladder is negative correlation.
7. one kind is used for the kit that the carcinoma of urinary bladder prognosis is judged, it is characterized in that, described kit is the excision tissue section that detects bladder cancer patients by immunohistochemistry technique, detects the expression of ATF3 albumen.
8. kit according to claim 7 is characterized in that, the prognosis of the expression of described ATF3 albumen and bladder cancer patients is proportionate life cycle.
9.ATF3 the application of albumen in the medicine that preparation inhibition carcinoma of urinary bladder shifts.
10.ATF3 albumen improves application in the medicine of prognosis life cycle of bladder cancer patients in preparation.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899953A (en) * | 2013-11-05 | 2016-08-24 | 新加坡科技研究局 | Bladder carcinoma biomarkers |
| CN107607712A (en) * | 2017-10-24 | 2018-01-19 | 李翀 | System for predicting bladder cancer patients chemosensitivity |
| CN111733244A (en) * | 2020-07-13 | 2020-10-02 | 北京化工大学 | Bladder cancer-depleted NKT cell subset, characteristic gene thereof and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008133766A1 (en) * | 2007-02-16 | 2008-11-06 | Pacific Arrow Limited | Blocking the migration or metastasis of cancer cells by affecting adhesion proteins and the uses of new compounds thereof |
| CN102443627A (en) * | 2004-08-10 | 2012-05-09 | 加的夫生物学有限公司 | Methods and kit for the prognosis of breast cancer |
-
2013
- 2013-04-27 CN CN2013101518390A patent/CN103235141A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102443627A (en) * | 2004-08-10 | 2012-05-09 | 加的夫生物学有限公司 | Methods and kit for the prognosis of breast cancer |
| WO2008133766A1 (en) * | 2007-02-16 | 2008-11-06 | Pacific Arrow Limited | Blocking the migration or metastasis of cancer cells by affecting adhesion proteins and the uses of new compounds thereof |
Non-Patent Citations (2)
| Title |
|---|
| XIANGLIANG YUAN 等: "ATF3 Suppresses Metastasis of Bladder Cancer by Regulating Gelsolin-Mediated Remodeling of the Actin Cytoskeleton", 《CANCER RESEARCH》, vol. 73, no. 12, 27 March 2013 (2013-03-27) * |
| 袁向亮 等: "新的膀胧癌转移抑制基因ATF3在膀胧癌中的表达意义及作用机制", 《 中华医学会第七次全国中青年检验医学学术会议论文汇编》, 3 May 2012 (2012-05-03) * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899953A (en) * | 2013-11-05 | 2016-08-24 | 新加坡科技研究局 | Bladder carcinoma biomarkers |
| US10509034B2 (en) | 2013-11-05 | 2019-12-17 | Agency For Science, Technology And Research | Bladder carcinoma biomarkers |
| CN107607712A (en) * | 2017-10-24 | 2018-01-19 | 李翀 | System for predicting bladder cancer patients chemosensitivity |
| CN111733244A (en) * | 2020-07-13 | 2020-10-02 | 北京化工大学 | Bladder cancer-depleted NKT cell subset, characteristic gene thereof and application thereof |
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Application publication date: 20130807 |