CN107727859A - A kind of serum I FN γ and LncRNAs composition is used for the purposes for preparing cancer diagnosis reagent box - Google Patents
A kind of serum I FN γ and LncRNAs composition is used for the purposes for preparing cancer diagnosis reagent box Download PDFInfo
- Publication number
- CN107727859A CN107727859A CN201710926251.6A CN201710926251A CN107727859A CN 107727859 A CN107727859 A CN 107727859A CN 201710926251 A CN201710926251 A CN 201710926251A CN 107727859 A CN107727859 A CN 107727859A
- Authority
- CN
- China
- Prior art keywords
- serum
- auc
- diagnosis
- purposes
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- G01N33/57446—Specifically defined cancers of stomach or intestine
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
It is used for the purposes for preparing cancer diagnosis reagent box the invention discloses a kind of serum I FN γ and LncRNAs composition.When serum I FN γ diagnosis differentiation stomach cancers are used alone with healthy volunteer, area (AUC) is 0.636 under ROC curve.It is a discovery of the invention that when distinguishing stomach cancer with healthy volunteer using serum NO level NHSAT089447 or NONHSAT041499 and serum I FN γ Combining diagnosis, AUC can bring up to 0.793 or 0.805；When distinguishing stomach cancer with healthy volunteer using serum NO level NHSAT089447 and NONHSAT041499 and serum I FN γ Combining diagnosis, AUC can bring up to 0.921.One skilled in the art will appreciate that area is between 1.0 and 0.5 under ROC curve, in AUC>In the case of 0.5, AUC illustrates that diagnosis effect is better closer to 1.AUC has relatively low accuracy at 0.5 0.7, and AUC has certain accuracy at 0.7 0.9, there is high accuracy when AUC is more than 0.9.Therefore, serum I FN γ can combine the diagnostic kit that serum NO level NHSAT089447 and/or NONHSAT041499 are used to prepare diagnosis of gastric cancer.
Description
Technical field
The invention belongs to gene diagnosis field, is related to the exploitation of diagnostic kit, and in particular to a kind of serum I FN- γ and
LncRNAs compositions are used for the purposes for preparing cancer diagnosis reagent box.
Background technology
Stomach cancer occupies malignant tumour the 2nd in China's incidence of disease, and death toll accounts for cancer occurrence numbers 14.33%, occupies the 3rd, only
Inferior to lung cancer and liver cancer.As can be seen here, stomach cancer is the emphasis for the treatment of and prevention of tumour.As tumor markers is widely used in clinic, more
Carry out more scholar's research and find that tumor markers plays an important role during prevention and control of cancer.IFN-γ is to participate in being immunized
The important cytokine of regulation, typically by the T lymphocytic emiocytosis activated, the growth of tumour cell can be influenceed.IFN-γ exists
Tumor patient Level of Expression of Retinoic Acid is substantially abnormal.Based on this, existing mark of the multinomial research using IFN-γ as diagnosing tumor.
Study and be used for diagnosis of gastric cancer (serum I FN- γ and tumor markers using serum I FN- γ as diagnosis marker
Joint-detection is to the diagnostic value of stomach cancer, biomedical engineering and clinical the 2nd phase of volume 20 in March, 2016), still, individually make
The degree of accuracy with serum I FN- γ diagnosis of gastric cancer is relatively low, and clinical value is low.
The content of the invention
It is used to prepare cancer diagnosis reagent box it is an object of the invention to provide serum I FN- γ and LncRNAs composition
Purposes, to improve the degree of accuracy of clinical diagnosis stomach cancer.
The present invention is achieved by following technical scheme：
IFN-γ and LncRNANONHSAT089447 or LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
Diagnosis composition purposes.
IFN-γ and LncRNANONHSAT089447, LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
The purposes of diagnosis composition.
Preferably, the IFN-γ, LncRNANONHSAT089447, LncRNANONHSAT041499 are serum I FN-
γ、NONHSAT089447、NONHSAT041499。
IFN-γ and LncRNANONHSAT089447 or LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
Diagnostic kit purposes.
IFN-γ and LncRNANONHSAT089447, LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
The purposes of diagnostic kit.
Preferably, the IFN-γ, LncRNANONHSAT089447, LncRNANONHSAT041499 are serum I FN-
γ、NONHSAT089447、NONHSAT041499。
Advantages of the present invention：
When serum I FN- γ diagnosis differentiation stomach cancers are used alone with healthy volunteer, area (AUC) is under ROC curve
0.636.It is a discovery of the invention that distinguished using serum NO level NHSAT089447 or NONHSAT041499 and serum I FN- γ Combining diagnosis
When stomach cancer is with healthy volunteer, AUC can bring up to 0.793 or 0.805；Using serum NO level NHSAT089447 and
When NONHSAT041499 distinguishes stomach cancer with healthy volunteer with serum I FN- γ Combining diagnosis, AUC can bring up to 0.921.This
Art personnel know that area is between 1.0 and 0.5 under ROC curve, in AUC>In the case of 0.5, AUC closer to 1,
Illustrate that diagnosis effect is better.AUC has relatively low accuracy in 0.5-0.7, and AUC has certain accuracy in 0.7-0.9, and AUC exists
There is high accuracy when more than 0.9.Therefore, serum I FN- γ can combine serum NO level NHSAT089447 and/or
NONHSAT041499 is used for the diagnostic kit for preparing diagnosis of gastric cancer.
Brief description of the drawings
Fig. 1 is that serum I FN- γ individually diagnose the ROC curve for distinguishing patients with gastric cancer and healthy volunteer；
Fig. 2 is that serum I FN- γ combine NONHSAT089447 diagnosis differentiation patients with gastric cancer and the ROC of healthy volunteer is bent
Line；
Fig. 3 is that serum I FN- γ combine NONHSAT041499 diagnosis differentiation patients with gastric cancer and the ROC of healthy volunteer is bent
Line；
Fig. 4 is that serum I FN- γ combine serum NO level NHSAT089447 and serum NO level NHSAT041499 diagnosis differentiation stomach cancer trouble
Person and the ROC curve of healthy volunteer.
Embodiment
Technical scheme is further described with reference to specific embodiment.
First, experiment material
Serum Obtained From Advance Gastric Cancer sample is derived from patient after the attached middle large hospital Surgery for Gastric Carcinoma of Southeast China University.All patients are preoperative
Do not receive the treatment such as radiotherapy, chemotherapy and antineoplastic, there is complete clinical and pathological data.Patients with gastric cancer
138 (stomach cancer groups), wherein women 63, male 75；Age 35-75 year, average age 63.3 years old.
Healthy volunteer's serum specimen 55 (Normal groups), wherein women 26, male 29；Age 35-70 year,
Average age 61.5 years old.
Age and sex composition no significant difference between stomach cancer group and Normal group.
IFN-γ detection Enzyme Linked Immunoadsorbent Assay (ELISA) kit is purchased from Raybiotech companies.
2nd, experimental method
1st, serum I FN- γ assay methods
IFN-γ detection uses ELISA method, illustrates strict implement according to kit.
2nd, serum LncRNAs assay methods
The μ L of serum 200 are taken, total serum IgE is extracted using the RNAprepPure kits of Tiangen companies.Should in experimentation
RNA degradeds are reduced as far as possible, to obtain the RNA that purity and quality are higher, are polluted without albumen and other impurity.With 1.5% fine jade
Sepharose electrophoretic analysis RNA integrality, ultraviolet spectrophotometry detection RNA concentration.
Use the 15 general reverse of TIANScript cDNA the first chain synthetic agent box and oligo (dT) of Tiangen companies
Record primer and carry out reverse transcription reaction.Reverse transcription total system is 20 μ L：1-5 μ g total serum IgEs, the μ L Super of 2 μ L oligo (dT) 15,2
Pure dNTPs, mend RNase-Free ddH2O to 14.5 μ L.Reaction tube put 70 DEG C heating 5min after rapidly in cooled on ice
2min, add 4 μ L 5X FIRST STRAND BUFFER (containing DTT), 0.5 μ L RNasin, 1 μ L TIANScriptM-
MLV, gently mixed with pipettor, 42 DEG C of warm bath 50min.95 DEG C of heating 5min terminating reactions, reaction product are standby in -20 DEG C of preservations
With.
According to Genbank objective gene sequences, designed with primer-design software primerpremier 5.0
NONHSAT089447, NONHSAT041499 specific primer, by Shanghai, Sheng Gong companies synthesize.Internal control primer HS-ACTB (β-
Actin Shanghai Sheng Gong companies) are purchased from.Reaction system (20 μ L)：The 2 μ L of μ L, cDNA of SYBR Select Master Mix 10, on
Swim the μ L of primer 1, anti-sense primer 1 μ L, ddH2O 6μL.Detected using the 7500FAST fluorescent quantitative detectors of ABI companies.
Response parameter：50℃2min；95 DEG C of 2min, 95 DEG C of 15s, 60 DEG C of 15s, 72 DEG C of 1min, totally 45 circulations.Solubility curve parameter：
95 DEG C of 15s, 60 DEG C of 1min, 95 DEG C of 15s, 60 DEG C of 15s.Every part of sample replication 3 times, obtain Ct values.With ACTB copy number
As correction radix, the relative internal reference expression quantity of each LncRNAs in each sample is calculated, is target LncRNAs in the sample
Relative expression quantity.
NONHSAT089447, NONHSAT041499 specific primer are as follows：
NONHSAT089447 upstreams：5’-GTAGGGCTTGGATGGACTTT-3’；
NONHSAT089447 downstreams：5’-CCGTCAACACATCAGGCCT-3’；
NONHSAT041499 upstreams：5’-CGATTTTGGGAACCTCTATC-3’；
NONHSAT041499 downstreams：5’-CAACTGCTGGGTGGAGTCTA-3’.
3rd, statistical procedures
Analyzed using the softwares of SPSS 20.0, represented with mean value ± deviation, compared between group and examined using t.Evaluation is every
Index application value, draw Receiver Operating Characteristics (ROC) curve, and area (AUC) under calculated curve；It is poor with P ＜ 0.05
It is different statistically significant.The diagnostic value of each single index and Joint Index to stomach cancer is evaluated using ROC curve.
3rd, experimental result
1st, between two groups Tumor Marker Levels comparison
IFN-γ level is significantly lower than Normal group in stomach cancer group serum, stomach cancer group serum NO NHSAT089447,
NONHSAT041499 relative expression levels are obviously higher than Normal group, and difference is statistically significant, and (t values are respectively
1.413rd, 2.034 and 1.935, P ＜ 0.01).Comparative result is as shown in table 1.
The comparison (mean value ± deviation) of Tumor Marker Levels between 1 two groups of table
2nd, tumor-marker analyte detection stomach cancer ROC curve is analyzed
When serum I FN- γ diagnosis differentiation stomach cancers are used alone with healthy volunteer, area (AUC) is under ROC curve
0.636.Stomach cancer and health are distinguished using serum NO level NHSAT089447 or NONHSAT041499 and serum I FN- γ Combining diagnosis
During volunteer, AUC can bring up to 0.793 or 0.805；Use serum NO level NHSAT089447 and NONHSAT041499 and serum
When IFN-γ triple combination diagnoses differentiation stomach cancer with healthy volunteer, AUC can bring up to 0.921, and accuracy rate is up to
92.23%.As can be seen here, serum I FN- γ combine NONHSAT089447 or NONHSAT041499 diagnosis of gastric cancer and had necessarily
Clinical value, serum I FN- γ joint NONHSAT089447 and NONHSAT041499 diagnosis of gastric cancer have higher clinical valency
Value.The ROC curve analysis of two or three indexs combines dualistic logistic regression and operated.
ROC curve analysis result is as shown in table 2 and Fig. 1-4.
The serum I FN- γ of table 2 are individually and joint NONHSAT089447 and/or NONHSAT041499 diagnostic values compare
One skilled in the art will appreciate that area is between 1.0 and 0.5 under ROC curve, in AUC>In the case of 0.5, AUC
Closer to 1, illustrate that diagnosis effect is better.AUC has relatively low accuracy in 0.5-0.7, and AUC fixes in 0.7-0.9
True property, there is high accuracy when AUC is more than 0.9.Therefore, serum I FN- γ can combine serum NO level NHSAT089447 and/or
NONHSAT041499 is used for the diagnostic kit for preparing diagnosis of gastric cancer.
Claims (6)
1.IFN- γ and LncRNANONHSAT089447 or LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
The purposes of diagnosis composition.
2.IFN- γ and LncRNANONHSAT089447, LncRNANONHSAT041499 combine for preparing examining for diagnosis of gastric cancer
The purposes of disconnected composition.
3. purposes according to claim 1 or 2, it is characterised in that：The IFN-γ, LncRNANONHSAT089447,
LncRNANONHSAT041499 is serum I FN- γ, NONHSAT089447, NONHSAT041499.
4.IFN- γ and LncRNANONHSAT089447 or LncRNANONHSAT041499 combine for preparing diagnosis of gastric cancer
The purposes of diagnostic kit.
5.IFN- γ and LncRNANONHSAT089447, LncRNANONHSAT041499 combine for preparing examining for diagnosis of gastric cancer
The purposes of disconnected kit.
6. the purposes according to claim 4 or 5, it is characterised in that：The IFN-γ, LncRNANONHSAT089447,
LncRNANONHSAT041499 is serum I FN- γ, NONHSAT089447, NONHSAT041499.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710926251.6A CN107727859B (en) | 2017-10-06 | 2017-10-06 | A kind of serum I FN- γ and LncRNAs composition is used to prepare the purposes of cancer diagnosis reagent box |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710926251.6A CN107727859B (en) | 2017-10-06 | 2017-10-06 | A kind of serum I FN- γ and LncRNAs composition is used to prepare the purposes of cancer diagnosis reagent box |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107727859A true CN107727859A (en) | 2018-02-23 |
| CN107727859B CN107727859B (en) | 2019-05-31 |
Family
ID=61209793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710926251.6A Expired - Fee Related CN107727859B (en) | 2017-10-06 | 2017-10-06 | A kind of serum I FN- γ and LncRNAs composition is used to prepare the purposes of cancer diagnosis reagent box |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107727859B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105586399A (en) * | 2015-09-07 | 2016-05-18 | 张国新 | Kit for serum/plasma lncRNA marker related to stomach cancer |
| CN106148529A (en) * | 2016-07-13 | 2016-11-23 | 中国人民解放军总医院 | The LncRNA label related to cancer of the stomach and special primer for checking, detection method, kit and application |
| CN106701900A (en) * | 2015-11-16 | 2017-05-24 | 上海市东方医院 | Long-chain noncoding RNA HERC2P3 gene and application thereof in gastric cancer |
| CN106755513A (en) * | 2017-02-08 | 2017-05-31 | 泰山医学院 | A kind of lncRNA marks of stomach cancer |
| CN106868204A (en) * | 2017-05-02 | 2017-06-20 | 北京泱深生物信息技术有限公司 | A kind of biomarker for sdenocarcinoma of stomach diagnosis |
| CN106906305A (en) * | 2017-05-02 | 2017-06-30 | 谷建斌 | Applications of the lncRNA in sdenocarcinoma of stomach diagnosis |
-
2017
- 2017-10-06 CN CN201710926251.6A patent/CN107727859B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105586399A (en) * | 2015-09-07 | 2016-05-18 | 张国新 | Kit for serum/plasma lncRNA marker related to stomach cancer |
| CN106701900A (en) * | 2015-11-16 | 2017-05-24 | 上海市东方医院 | Long-chain noncoding RNA HERC2P3 gene and application thereof in gastric cancer |
| CN106148529A (en) * | 2016-07-13 | 2016-11-23 | 中国人民解放军总医院 | The LncRNA label related to cancer of the stomach and special primer for checking, detection method, kit and application |
| CN106755513A (en) * | 2017-02-08 | 2017-05-31 | 泰山医学院 | A kind of lncRNA marks of stomach cancer |
| CN106868204A (en) * | 2017-05-02 | 2017-06-20 | 北京泱深生物信息技术有限公司 | A kind of biomarker for sdenocarcinoma of stomach diagnosis |
| CN106906305A (en) * | 2017-05-02 | 2017-06-30 | 谷建斌 | Applications of the lncRNA in sdenocarcinoma of stomach diagnosis |
Non-Patent Citations (3)
| Title |
|---|
| KECHENG ZHANG: "Genome-wide LncRNA microarray profiling identifies novel circulating LncRNAs for detection of gastric cancer", 《THERANOSTIC》 * |
| 沈东杰: "血清IFN-γ和肿瘤标志物联合检测对胃癌的诊断价值", 《生物医学工程与临床》 * |
| 赵久达，徐兵河: "长链非编码RNA与胃癌发生、发展、诊治及预后关系的研究关系", 《中华医学杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107727859B (en) | 2019-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6759217B2 (en) | Method enabling use of extracellular RNA extracted from plasma or serum to detect, monitor or evaluate cancer | |
| CN110484624B (en) | Gastric cancer biomarker based on peripheral blood and detection method and application thereof | |
| CN111826444A (en) | Serum/plasma tsRNA marker related to pancreatic cancer, probe and application thereof | |
| CN101709328A (en) | Serology biological marker for detecting tumor of breast and application thereof | |
| CN107254546B (en) | SNP marker related to breast cancer neoadjuvant chemotherapy curative effect and application thereof | |
| CN114292920B (en) | Group of gastric precancerous lesions and gastric early diagnosis plasma RNA marker combination and application | |
| CN108796082B (en) | Use of long-chain non-coding RNAs | |
| KR20210105155A (en) | Biomarker for diagnosis of cancer and use thereof | |
| CN107727859A (en) | A kind of serum I FN γ and LncRNAs composition is used for the purposes for preparing cancer diagnosis reagent box | |
| CN116287255A (en) | Pancreatic cancer diagnosis kit | |
| CN102851354B (en) | Primer pair and kit for detecting methylation state of DNA at cell DACH1 gene promoter region | |
| KR20150102468A (en) | Lung Cancer Diagnotic kit comprising primer set and probe for mutation related to lung cancer | |
| KR101441013B1 (en) | Biomarker for diagnosing breast cancer | |
| CN109182514A (en) | Pulmonary cancer diagnosis or transfer diagnosis marker LncRNA Loc729658 and kit and its application | |
| CN106282360B (en) | A kind of blood plasma miRNA combination, its probe compositions and application for colon cancer prediction transfer | |
| CN113355420B (en) | JAK3 promoter methylation detection primer composition, application and detection method | |
| John et al. | Role of red cell distribution width and other blood cell indices in differentiating between benign and malignant diseases of gallbladder | |
| CN104878012B (en) | Applications of the 5p of Hsa miR 3200 in preparing early screening or diagnosing Brachyury positive tumors reagent or kit | |
| CN108676888B (en) | Reagent kit and system for predicting susceptibility of lung malignant tumor | |
| CN104762387A (en) | Application of single nucleotide polymorphism rs17083838 in detection of pituitary adenoma | |
| CN108676890B (en) | Female breast malignant tumor susceptibility prediction kit and system | |
| CN108841959B (en) | Kit and system for predicting susceptibility of oral cavity and head and neck malignant tumors | |
| CN111705133B (en) | Application of LncRNAs in preparation of primary liver cancer early diagnosis kit | |
| CN108676891B (en) | Rectal adenocarcinoma susceptibility prediction kit and system | |
| CN108676889B (en) | Gastric adenocarcinoma susceptibility prediction kit and system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20190301 Address after: 211505 D building, 9 Chuang Chuang Road, Zhongshan science and Technology Park, Liuhe District, Nanjing, Jiangsu. Applicant after: Cui Changyou Address before: 211198 1009 Tianyuan East Road, Gao Xin Garden, Jiangning District, Nanjing, Jiangsu. Applicant before: Nanjing fluoro Biological Detection Technology Co., Ltd. |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20190507 Address after: Room F7, Fifth Floor, 155 Futexi Road, China (Shanghai) Free Trade Pilot Area, Pudong New Area, Shanghai, 200120 Applicant after: SHANGHAI HEDUN BIOTECHNOLOGY CO., LTD. Address before: 211505 D building, 9 Chuang Chuang Road, Zhongshan science and Technology Park, Liuhe District, Nanjing, Jiangsu. Applicant before: Cui Changyou |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190531 Termination date: 20201006 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |