CN108196071A - liver cancer serum marker NRP1 - Google Patents
liver cancer serum marker NRP1 Download PDFInfo
- Publication number
- CN108196071A CN108196071A CN201810134554.9A CN201810134554A CN108196071A CN 108196071 A CN108196071 A CN 108196071A CN 201810134554 A CN201810134554 A CN 201810134554A CN 108196071 A CN108196071 A CN 108196071A
- Authority
- CN
- China
- Prior art keywords
- nrp1
- liver cancer
- serum
- marker
- liver
- 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.)
- Pending
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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
Abstract
The present invention relates to the new applications of NRP1, i.e. NRP1 is as liver cancer serum marker.Its advantage is shown：It is a discovery of the invention that NRP1 is the direct target gene of TEAD, NRP1 promotes liver cancer, and liver cancer patient blood serum NRP1 levels are higher, and liver cancer patient blood serum NRP1 levels are related to most liver function indexs.Present invention discover that the excellent diagnostics threshold value of serum N RP1 prediction liver cancer is 68pg/ml, sensitivity 93.7%, specificity is 98.7%, and it is preferable diagnosis marker in liver cancer to illustrate serum N RP1.
Description
Technical field
The present invention relates to laboratory medicine technical field, specifically, being a kind of liver cancer serum marker.
Background technology
NRP1 is a kind of I types transmembrane glycoprotein, is initially found in neural axon guiding and embryonic blood vessel generation and plays
Effect.NRP1 can promote tumorigenic angiogenesis, cell survival, migration, invasion and chemical resistant.In recent years, NRP1
It is found to be the key obstacle of antineoplastic immune.Ligand semaphorin-4a (Sema4a) phase that NRP1 is expressed with immunocyte
Interaction enhances the function of regulatory T cells (Tregs) and survival in tumour, and then limits anti tumor immune response.In addition,
The progress that NRP1 slows down glioma is knocked out from the macrophage of microglia or derived from bone marrow.NRP1 may be that cancer is controlled
The target for the treatment of.It is reported that MNRP1685A is the monoclonal antibody of NRP1, good effect is shown in clinical test.NRP1
Micromolecular inhibitor, such as EG00229 can also slow down tumour progression.In research before, We conducted ChIP-seq
Analysis, data show that NRP1 may be a new target gene for promoting cancer transcription factor TEAD in cancer cell.However, NRP1 is
No stimulation tumour occurs and is used as the novel tumor markers in liver cancer still unknown.
At present, serum tumor marker detection such as alpha-fetoprotein (AFP) have been used for early diagnosis of tumor, assessment prognosis and
Observe curative effect recurrence and transfer etc..Chinese patent literature CN107326066A discloses in urine NRP1 as carcinoma of urinary bladder
Diagnosis marker.But the NRP1 about the present invention yet there are no report as the blood serum tumor markers of liver cancer.
Invention content
First purpose of the present invention is, for deficiency of the prior art, to provide a kind of new application of NRP1.
Second object of the present invention is to provide a kind of new application of NRP1 inhibitor.
To realize above-mentioned first purpose, the technical solution adopted by the present invention is that：Diagnosis mark of the NRP1 albumen as liver cancer
The application of will object.
Application of the NRP1 albumen as the blood serum designated object of liver cancer.
Application of the NRP1 albumen as marker in the detection product for preparing diagnosing liver cancer.
NRP1 albumen as marker prepare to liver cancer by stages detection product in application.
NRP1 albumen is as blood serum designated object.
The detection product testing serum.
The detection product is diagnostic kit.
NRP1 albumen is as unique marker.
To realize above-mentioned second purpose, the technical solution adopted by the present invention is that：The inhibitor of NRP1 genes or albumen exists
Prepare the application in the drug for the treatment of liver cancer.
The invention has the advantages that：
1st, it is a discovery of the invention that NRP1 is the direct target gene of TEAD, NRP1 promotes liver cancer, liver cancer patient blood serum NRP1
Horizontal higher, liver cancer patient blood serum NRP1 levels are related to most liver function indexs.
2nd, present invention discover that the excellent diagnostics threshold value of serum N RP1 prediction liver cancer is 68pg/ml, sensitivity 93.7% is special
The opposite sex is 98.7%, and it is preferable diagnosis marker in liver cancer to illustrate serum N RP1.
Description of the drawings
Attached drawing 1：NRP1 is the direct target genes of TEAD.
Attached drawing 2：NRP1 can promote liver cancer.
Attached drawing 3：Liver cancer patient blood serum NRP1 specificity increases.
Attached drawing 4：Liver cancer patient blood serum NRP1 levels are related to a variety of liver function indexs.
Attached drawing 5：Serum N RP1 is an advantage over the liver cancer marker of AFP.
Specific embodiment
It elaborates with reference to embodiment to specific embodiment provided by the invention.
Sample is collected
All samples are collected in Shanghai City Ruijin Hospital in May, 2015 to during in November, 2016.Liver cancer patient average year
Age is 55.37 ± 8.63 years old, male to female ratio 2.35:1, hepatitis B patient average age, 38.66 ± 6.44 years old；Male to female ratio
1.35:1, hepatitis C patients average age, 57.45 ± 11.03 years old；Male to female ratio 1.2:1, liver cirrhosis patient average age
58.04 ± 9.66 years old；Male to female ratio is 2.83:1, colorectal cancer patients average age 55.66 ± 11.44 years old, male to female ratio 3.75:
1, patients with lung cancer average age 52.37 ± 2.45 years old, male to female ratio 3.9:1, patients with gastric cancer is 59.24 ± 12.06 years old average, men and women
Ratio 3.75:1, patient with breast cancer's average age 38.49 ± 13.73 years old；It is female patient.All patients, which obtain, to know together
Meaning book.Diagnosing cancer of liver result is confirmed by computed tomography and magnetic resonance imaging.Histopathological analysis is carried out to confirm
With colon cancer, gastric cancer, the diagnostic result of the patient of breast cancer and lung cancer.B-mode or hepatitis C patients are examined in serum respectively
It measures more than 1 × 103HBV the or HCV DNA (China of section, Shanghai, China) of copy.Simultaneously in May, 2015 in November, 2016,
Having recruited 80 healthy volunteers in Shanghai Ruijin Hospital, (average age is 53.72 ± 13.88 years old, male to female ratio 1.35:1)
As a control group.Metastatic hepatic neoplasm patient is not included in our current research.Liver function index is measured using automatic biochemistry analyzer
[transaminase (AST and ALT), alkaline phosphatase (ALP), albumin (Alb), total bilirubin, total protein, bile acid, prealbumin
(pre-Alb) and gamma glutamyl transpeptidase (γ-GT)].Research approach according to the codes of ethics of Declaration of Helsinki in 1975 into
Row.
Cell is bought
Liver cancer cell lines and normal liver cell are purchased from Chinese Academy of Sciences's cell bank.TEAD expression plasmids, TEAD-shRNA and
NRP1-shRNA is purchased from Aureal genome company (Beijing, China).PCR amplification obtains open country from the genome of Bel-7402 cells
Raw type (WT)-NRP1- promoter plasmids, and be cloned into pGL4.21 (Promega, Madison, WI, USA) carrier.Make
Saltant type (Mut)-NRP1- promoter plasmids are built with over-lap PCR.
Immunohistochemistry
Human liver cancer tissue microarray slide is acted on behalf of (Chinese Xi'an) by Alenabio and is bought from Biomax companies of the U.S..
Histotomy is taken off into paraffin and rehydration first.Then, using the Tris-EDTA buffer solutions of pH 6.0 (the green skies, Haimen, in
State) antigen retrieval is carried out at 100 DEG C 2 hours.Using 3% peroxide by endogenous peroxydase close 20 minutes, so
It closes in Block buffer (5%BSA+0.1%Triton X-100) and is incubated overnight together with primary antibody afterwards.It is used in IHC
Main antibody be anti-NRP1 (Abcam, Hong-Kong, #ab81321).With Vectastain ABC kits (Vector
Labs, Burlingame, CA, USA) detection signal.
Immunoblot experiment
Cell protein lysate is detached and is transferred on nitrocellulose filter in sds page.By film
It closes in Block buffer (5% milk in the Tris buffered salines containing 0.5% tween), is then incubated with specific antibody
It educates.Used primary antibody is anti-GAPDH [Cell Signaling Technology (CST), Boston, MA, #5174], anti-
TEAD (Abcam, #ab197589), anti-NRP1 (Abcam, #ab81321), anti-YAP (Abcam, #ab52771), anti-TAZ
(Abcam, #ab84927) and anti-c-Jun (Abcam, #ab31419).
QPCR and fluorescence carrier reporter assay
Total serum IgE is detached from cell, and use PrimeScript using Trizol (Ambion, Carlsbad, CA, USA)
Kit (Perfect Real Time) (TaKaRa, Dalian, China) reverse transcription.With SYBR premix Ex Taq
(TaKaRa) cDNA as obtained by quantitative PCR analysis.Luciferase reporter vector steadily expresses matter with renilla luciferase
In grain cotransfection to Bel-7402 and SMMC-7721 cells.Luciferin enzyme activity is detected using Dual-Luciferase reagent (Promega)
Property.
Measurement cell viability, Caspase-3/7 are active and soft-agar cloning is formed
The cell viability for being based on Methyl thiazole tetrazole (MTT) is measured, by cell with the density of every 3000 cells in hole
It is seeded in 96 orifice plates.After 5 days, cell is handled, and exist after 4 hours with the MTT reagents (Sangon, Chinese Shanghai) of 5mg/mL
It is cracked in DMSO.Absorbance is measured at 595nm.For the determination of activity of Caspase-3/7, by cell with every hole 104It is a thin
The density of born of the same parents is seeded in 96 orifice plates of white, and measures half using Caspase-3/7Glo measurement systems (Promega)
3/7 activity of Guang aspartase.For soft-fractrue rock mass measure, by cell with the density of every 6000 cells in hole be seeded in containing
In 6 orifice plates of 10%FBS in the DMEM of 0.3% agarose.After two weeks, with the bacterium colony in 12 visuals field of microscopic counting.
Enzyme-linked immunosorbent assay (ELISA)
Enzyme-linked immunosorbent assay is carried out to assess the concentration of Serum AFP and NRP1.By blood serum sample in dilution buffer
Middle dilution (1：4), and by the diluted sample/holes of 50 μ l it is added to progress AFP and NRP1 concentration analysis in 96 hole microtiter plates.
ELISA kit is purchased from Lichen Biotech Co., Ltds (Chinese Shanghai).It is carried out in strict accordance with the guideline of manufacturer
Analysis.Signal is determined by measuring the absorbance at 450nm.
Statistical analysis
Using independent samples t test, variance analysis, Mann-Whitney is examined, Wilcoxon label rank sum tests and
Kruskal-Wallis examines continuous variable difference between comparative group.Spearman grades related check is carried out to calculate grade variables
Between related coefficient.NRP1, AFP and NRP1 and AFP associated prediction liver are assessed using area under ROC curve (AUC-ROC)
The diagnostic value of cancer.We determine diagnostic threshold by ROC curve.P<0.05 is considered being statistically significant.
Hereafter abbreviated with well known to those skilled in the art：
AFP, alpha-fetoprotein；γ-GT, gamma glutamyl transpeptidase；Alb, albumin；ALT, glutamic-pyruvic transaminase；AST, millet straw
Transaminase；ALP, alkaline phosphatase；Pre-Alb, prealbumin.
Embodiment 1：NRP1 is the direct target gene of TEAD
The ChIP-seq analysis predictions NRP1 studied before may be the direct target gene of TEAD.Therefore, We conducted
Whether a series of experiments further determines that the NRP1 by TEAD direct regulations and controls.QPCR data show, two kinds of liver cancer of high carcinogenic
In cell line Bel-7402 and SMMC-7721, TEAD is overexpressed the mRNA level in-site for increasing NRP1, and TEAD strikes low reduce
The mRNA level in-site (Figure 1A) of NRP1.Similarly, the protein level of NRP1 also with the expression positive correlation of TEAD (Figure 1B).It is worth note
Meaning identifies conservative TEAD binding motifs (Fig. 1 C) in the region of nucleotide -1848~-1841 of NRP1 promoters.
By the uciferase activity for testing WT- and motif mutant (Mut-) NRP1 promoters, it has been found that the startup of NRP1 genes
Sub- activity is promoted by TEAD, and TEAD loses enhancing NRP1 promoter luciferase activities when TEAD binding motifs are removed
Ability (Fig. 1 D).These are the result shows that TEAD is bonded directly in the promoter of NRP1 turn with stimulate it in liver cancer cells
Record.
Embodiment 2：NRP1 promotes liver cancer
30 normal liver tissue samples and 40 hepatoma samples are tested by using tissue microarray assay, find NRP expression
The up-regulation (Fig. 2A) more notable than normal structure in liver cancer tissue.Moreover, NRP1 is raised on cell membrane into liver cancer tissue, and
The protein (Fig. 2A) is not detected in the normal tissue.In addition, compared with normal liver cell system HL-7702, in liver cancer cells
Higher levels of NRP1 (Fig. 2 B) is detected in system.We have also observed that the notable association (figure between NRP1 and TEAD expression
2B).It is well known that NRP1 is responsible for the angiogenesis of tumour.Next, we test whether liver cancer cells malignant phenotype needs
NRP1 genes.We employ the shRNA (Fig. 2 C) of two kinds of independent efficient targeting NRP1.It is observed that striking low NRP1 can press down
Liver cancer cells vigor (Fig. 2 D) processed and Colony forming (Fig. 2 E-F), while raise Apoptosis marker Caspase-3/7
Active (Fig. 2 G).These are statistics indicate that NRP1 height is expressed and promotes liver neoplasm.
Embodiment 3：Liver cancer patient blood serum NRP1 levels are higher
Use immunoblotting assay liver cancer patient and the protein expression level of the blood serum sample of healthy individuals.Anti- NRP1 antibody
The specific band to 103kDa is found in the blood serum sample of liver cancer patient, and is not detected in healthy individuals similar
Band (Fig. 3 A).Since NRP1 is regulated and controled by TEAD, we be also tested in blood serum sample whether detect TEAD or its directly
Binding protein, such as YAP, TAZ and c-Jun.But, these bands do not detect in liver cancer patient or the serum of healthy individuals
It arrives, although showing that these TEAD GAP-associated protein GAPs play a crucial role in liver cancer development, they cannot act as liver tumour marker
(Fig. 3 A).We also measure Healthy People and other hepatopathys (including hepatitis B/hepatitis and hepatic sclerosis), other kinds of digestive system
Cancer (including colon cancer and gastric cancer) and breast cancer and the concentration of Serum of Patients with Lung Cancer NRP1 are with the serum of determining high concentration
Whether NRP1 is liver cancer-specific.We have found that liver cancer patient blood serum NRP1 concentration (956.464 ± 563.869pg/ml, n=
104) it is significantly higher than healthy individuals (28.872 ± 13.241pg/ml, n=80, p=0.000), hepatitis B patient (73.361 ±
32.905pg/ml, n=33, p=0.000), hepatitis patient (60.009 ± 18.007pg/ml, n=26, p=0.000), liver is hard
Change patient (75.614 ± 30.902pg/ml, n=23, p=0.000), patient with breast cancer (62.275 ± 23.627pg/ml, n=
22, p=0.000), colorectal cancer patients (68.844 ± 27.929pg/ml, n=40, p=0.000), patients with gastric cancer (61.010 ±
34.981pg/ml, n=19, p=0.000) and patients with lung cancer (47.492 ± 32.505pg/ml, n=21, p=0.000) (figure
3B).In addition, higher NRP1 concentration and higher neoplasm staging in liver cancer are significantly correlated (Fig. 3 C).
Embodiment 3：The relationship of liver cancer patient blood serum NRP1 levels and liver function index
Serum alpha-fetoprotein (AFP) is liver cancer classics marker.The distribution of the scatterplot of serum N RP1 and Serum AFP shows serum
It is proportionate between NRP1 and Serum AFP (R=0.686, P=0.000, Fig. 4 A).We have also investigated serum N RP1 levels with
Relationship between liver function index.The results show that serum N RP1 levels and γ-GT (R=0.411, P=0.000, Fig. 4 B), Alb
(R=-0.445, P=0.000, Fig. 4 C), bile acid (R=0.313, AST (R=0.646, p=0.000, Fig. 4 F), ALP (R=
0.430, p=0.000, Fig. 4 D), ALT (R=0.527, p=0.000, Fig. 4 G) and pre-Alb (R=-0.359, p=0.001,
Fig. 4 H).However, serum N RP1 levels and total bilirubin (R=0.231, p=0.118, Fig. 4 I) or total protein (R is not observed
=0.042, p=0.788) between significant correlation.
Embodiment 5：Serum N RP1 is preferable diagnosis marker in liver cancer
AUC-ROC analysis shows, with AFP (AUC：0.862,95%CI：It 0.806-0.918) compares, serum N RP1 (AUC：
0.971,95%CI：0.947-0.994) it is better diagnosing cancer of liver marker.The excellent diagnostics threshold value for predicting liver cancer is 68pg/
Ml, sensitivity 93.7%, specificity are 98.7% (Fig. 5).AUC-ROC analyses are it is also shown that NRP1 and AFP Combining diagnosis liver cancer
(AUC：0.983,95%CI：0.968-0.998) only it is slightly better than NRP1.It swells these results indicate that NRP1 is used alone as liver
It is feasible that tumor markers, which are applied to clinic,.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, under the premise of the method for the present invention is not departed from, can also make several improvement and supplement, these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (9)
- Application of the 1.NRP1 albumen as the diagnosis marker of liver cancer.
- Application of the 2.NRP1 albumen as the blood serum designated object of liver cancer.
- Application of the 3.NRP1 albumen as marker in the detection product for preparing diagnosing liver cancer.
- 4.NRP1 albumen as marker prepare to liver cancer by stages detection product in application.
- 5. application according to claim 3 or 4, which is characterized in that NRP1 albumen is as blood serum designated object.
- 6. application according to claim 3 or 4, which is characterized in that the detection product testing serum.
- 7. application according to claim 3 or 4, which is characterized in that the detection product is diagnostic kit.
- 8. application according to claim 3 or 4, which is characterized in that NRP1 albumen is as unique marker.
- Application of the inhibitor of 9.NRP1 genes or albumen in the drug for preparing treatment liver cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810134554.9A CN108196071A (en) | 2018-02-09 | 2018-02-09 | liver cancer serum marker NRP1 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810134554.9A CN108196071A (en) | 2018-02-09 | 2018-02-09 | liver cancer serum marker NRP1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108196071A true CN108196071A (en) | 2018-06-22 |
Family
ID=62593673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810134554.9A Pending CN108196071A (en) | 2018-02-09 | 2018-02-09 | liver cancer serum marker NRP1 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108196071A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113773394A (en) * | 2020-06-10 | 2021-12-10 | 山东大学 | Fusion peptide and application thereof in preparation of anti-tumor preparation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020039731A1 (en) * | 1999-01-15 | 2002-04-04 | Stuart Susan G. | Ndr2-related proteins |
| CN101326196A (en) * | 2005-11-08 | 2008-12-17 | 健泰科生物技术公司 | Neuropilin antagonists |
| WO2009099959A2 (en) * | 2008-01-31 | 2009-08-13 | The Board Of Regents Of Teh University Of Texas System | Tumor cell expression of neuropilin as a target for cancer therapy |
-
2018
- 2018-02-09 CN CN201810134554.9A patent/CN108196071A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020039731A1 (en) * | 1999-01-15 | 2002-04-04 | Stuart Susan G. | Ndr2-related proteins |
| CN101326196A (en) * | 2005-11-08 | 2008-12-17 | 健泰科生物技术公司 | Neuropilin antagonists |
| WO2009099959A2 (en) * | 2008-01-31 | 2009-08-13 | The Board Of Regents Of Teh University Of Texas System | Tumor cell expression of neuropilin as a target for cancer therapy |
Non-Patent Citations (5)
| Title |
|---|
| BERGE M等: "Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling", 《JOURNAL OF HEPATOLOGY》 * |
| GÜLSÜM ÖZLEM ELPEK: "Neuropilins and liver", 《WORLD J GASTROENTEROL》 * |
| XU J等: "NRP-1 silencing suppresses hepatocellular carcinoma cell growth in vitro and in vivo", 《EXPERIMENTAL AND THERAPEUTIC MEDICINE》 * |
| ZHANG Y等: "High Expression of Neuropilin-1 Associates with Unfavorable Clinicopathological Features in Hepatocellular Carcinoma", 《PATHOLOGY & ONCOLOGY RESEARCH》 * |
| 郭银燕等: "应用基因芯片技术研究肝癌组织特异性候选基因", 《江苏医药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113773394A (en) * | 2020-06-10 | 2021-12-10 | 山东大学 | Fusion peptide and application thereof in preparation of anti-tumor preparation |
| CN113773394B (en) * | 2020-06-10 | 2023-10-27 | 山东大学 | Fusion peptide and application thereof in preparation of antitumor preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zamanova et al. | Carbonic anhydrases as disease markers | |
| Hoang et al. | Expression of LDL receptor‐related protein 5 (LRP5) as a novel marker for disease progression in high‐grade osteosarcoma | |
| Gongoll et al. | Prognostic significance of calcium-binding protein S100A4 in colorectal cancer | |
| US9797905B2 (en) | Use of markers in the diagnosis and treatment of prostate cancer | |
| JP6138154B2 (en) | Biomarkers for breast cancer prediction and diagnosis | |
| Wu et al. | Protein tyrosine-phosphatase expression profiling in gastric cancer tissues | |
| Hsueh et al. | Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma | |
| Dolderer et al. | HERG1 gene expression as a specific tumor marker in colorectal tissues | |
| Kowalczyk et al. | Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal cancer and normal tissues | |
| Ciribilli et al. | Oncogenomics of c-Myc transgenic mice reveal novel regulators of extracellular signaling, angiogenesis and invasion with clinical significance for human lung adenocarcinoma | |
| JP5773315B2 (en) | CXCL4L1 as a biomarker for pancreatic cancer | |
| Lin et al. | ADAM9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma | |
| CN108196071A (en) | liver cancer serum marker NRP1 | |
| TWI399541B (en) | Method for prognosis of gastric cancer | |
| KR101058753B1 (en) | Characterization of ESM-1 as a tumor associated marker of colorectal cancer | |
| KR20180030347A (en) | A marker for diagnosis of lung cancer | |
| KR102006999B1 (en) | A composition for diagnosing colon cancer metastasis or predicting the same, and use thereof | |
| Köditz et al. | Novel noninvasive marker of regression of clear cell renal cell carcinoma (ccRCC) | |
| Mylona et al. | Study of the topographic distribution of ets-1 protein expression in invasive breast carcinomas in relation to tumor phenotype | |
| ES2339125T3 (en) | SP1 PHOSPHORILED AS A MARKER IN THE DIAGNOSIS OF NON-ALCOHOLIC ESTEATOHEPATITIS (EHNA) AND DIANA IN THE SCREENING OF PHARMACOS FOR EHNA. | |
| WO2013096852A1 (en) | Biomarkers of cancer | |
| KR102026252B1 (en) | The biomarker for lung Squamous cell carcinoma and Diagnosis method for lung Squamous cell carcinoma using thereof | |
| US20230019818A1 (en) | Methods of detecting and treating hpv-positive head and neck squamous cell carcinoma | |
| KR102199001B1 (en) | A novel biomarker for diagnosing liver cancer | |
| Ghassemi et al. | Positive Association of Matrix Proteins Alteration with TAZ and The Progression of High-Grade Bladder Cancer |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180622 |
|
| RJ01 | Rejection of invention patent application after publication |