CN106645723A - Application of Shp2 protein in preparation of kit for evaluating therapeutic effect of sorafenib on liver cancer - Google Patents
Application of Shp2 protein in preparation of kit for evaluating therapeutic effect of sorafenib on liver cancer Download PDFInfo
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Abstract
The invention belongs to the technical field of biology. The expression quantity of Shp2 protein in liver cancer tissues is detected by adopting an immunohistochemical method so as to determine the sensitivity of liver cancer patients on sorafenib. The invention provides an application of Shp2 protein in the preparation of a kit for evaluating the therapeutic effect of sorafenib on liver cancer. The Shp2 protein is used as a protein molecular marker for determining the therapeutic effect of sorafenib on the liver cancer, and has an important guiding significance for a liver cancer patient as whether to use sorafenib for treatment or not.
Description
Technical field
The present invention relates to biological technical field, is related to a kind of application of Shp2 albumen, it is that Shp2 albumen is being made specifically
Standby liver cancer is to the application in Sorafenib curative effect evaluation kit.
Background technology
Primary carcinoma of liver is one of modal malignant tumour in the world, and wherein hepatocellular carcinoma (HCC) account for 90% or so.
With according to " global newest cancer statistics is announced " data display, there are 78.2 ten thousand new cases in the whole world within 2012, and 74.5 ten thousand is dead
Case.Wherein, Chinese neopathy number of cases and death number account for only about half of, and primary carcinoma of liver has become China the
Two big lethal malignant tumours.
In recent years, the research for treating liver cancer using molecular targeted agents is gradually taken seriously, and is becoming new focus.It is many
Multi-targeted receptor tyrosine kinase inhibitor Sorafenib (Nexavar) is currently the only one to be ratified for liver cancer molecular target by FDA
To the medicine for the treatment of, but recent study find Sorafenib in patient reactivity than relatively low, only small part patient energy
Enough real benefits.Quite a few clothes for patients Sorafenib is not only without effect, and side effect is larger.It was found that effectively prediction
The biomarker of Sorafenib curative effect is come the problem that instructs Sorafenib clinical application to be urgent need to resolve.
This area can predict Sorafenib in liver cancer postoperative adjuvant therapy target spot related gene or albumen in the urgent need to finding,
The research of this respect is to clinical treatment liver cancer and instructs Sorafenib clinical application significant.
Shp2 (English full name：Protein tyrosine phosphatase, non-receptor type 11) by base
Because of PTPN11 (GeneID：5781) it is coded, be a kind of non-transmembrane Protein-tyrosine-phosphatase, its N-terminal contain 2 it is identical
SH2 domains, Shp2 combines phosphotyrosine by SH2 domains so as to the tyrosine phosphatase in self structure
(PTP enzymes) is activated, and dephosphorylized effect is played (referring to document to intracellular other signaling molecules：Alonso A., Sasin
J., Bottini N., et al.Protein tyrosine phosphatases in the human genome, Cell
2004；117：699-711).In general protein kinase promotes signal transmission, and protein phosphatase enzyme level signal transmission；And
Not only the special character of Shp2 is just being that its dephosphorylation effect does not suppress but also promote signal transmission, and then thin adjusting
Play an important role in the biological multi-signal transductive process of born of the same parents and control cytoactive.
More in recent years experimental studies have found that Shp2 molecules and its mutant have pass closely with various malignant diseases
System, in spatial abnormal feature and overexpression in Hematopoietic Malignancies, this process is considered as Shp2 ginsengs to document report Shp2
Signal such as IL-3 (interleukin-13), PDGF (platelet-derived growth factor), the GM- produced with the transducer cell outgrowth factor
CSF (colony stimulating factor) etc., and forward direction adjusts the letter such as Ras/Erk, PI3K/Akt and Jak/STAT relevant with cell propagation
Number Signal Transduction Pathways are (referring to document：Chen J., Yu W.M., Daino H., et al.SHP-2phosphatase is
required for hematopoietic cell transformation by Bcr-Abl.Blood 2007；109：778-
785)。
It is recognized as having played weight to Shp2 Protein Gs ab2 in connection during cancerous cell transformation in gastric epithelial cell
Act on (referring to document：Golam Mohi M., Benjamin G.N.The role of Shp2 (PTPN11) in cancer,
Current Opinion in Genetics&Development2007；17：23-30).Research also shows Shp2 and Gab2 ginsengs
With abnormal activation galactophore epithelial cell HER2/Neu paths, cause galactophore epithelial cell conversion with canceration (referring to document：
Bentires-Alj M., Gii S.G., Chan R., et al.Casual role of the scaffolding adapter
Gab2in breast cancer, Nature Medicine2006；12：114-121).
In the research of liver diseases, Shp2 to be reported and promote liver by adjusting the paths such as Erk, Akt and IL-6/STAT3
Hepatocellular regeneration after damage.Our research finds that Shp2 is expressed in most of liver cancer in high, and can promote the life of liver cancer
Long and transfer is (referring to document：Bard-Chapeau E.A., YuanJ., Droin N., et al.Concerted Functions
Of Gab1and Shp2in Liver Regeneration and Hepatoprotection, Molecular and
Cellular Biology.2006；26：4664-4674.).Clinical and Pathological Analysis show patient's good prognosis of Shp2 low expressions；
Patient to taking Sorafenib treatment is analyzed the patient's good prognosis it has been found that Shp2 low expressions.But, Shp2 is low
Whether the prognosis compared with Sorafenib is not taken of the clothes for patients Sorafenib of expression has difference, that is to say, that Shp2 low expressions
Patient whether report there is no to Sorafenib sensitivity.
Yet there are no the research report answered of the Shp2 albumen in liver cancer Sorafenib curative effect evaluation kit is prepared.
The content of the invention
It is an object of the invention to provide the new opplication of Shp2 albumen, particularly comments Sorafenib curative effect in preparation liver cancer
Estimate the application in kit.
The present inventor is had found first through extensively in-depth study, is existed using ImmunohistochemistryMethods Methods detection Shp2 albumen
The expression in Sorafenib patient's liver cancer tissue is taken after Liver Cancer Operation, can interpolate that postoperative liver cancer patient for Sorafenib medicine
The sensitiveness of thing.This correlation of the expression based on Shp2 albumen and liver cancer, using the albumen as molecular target, to its table
Carry out detecting up to amount and can be used for the judge index that postoperative hepatocarcinoma patient takes Sorafenib.
A first aspect of the present invention, there is provided Shp2 albumen Sorafenib curative effect evaluation reagent or reagent after Liver Cancer Operation is prepared
Application in box.
Expression of the described reagent or kit detection Shp2 albumen in liver cancer tissue.
Preferably, described reagent or kit detect table of the Shp2 albumen in liver cancer tissue using ImmunohistochemistryMethods Methods
Up to amount.
It is furthermore preferred that described reagent or kit are as molecular labeling using Shp2 albumen, it is anti-using Shp2 monoclonals
Body or polyclonal antibody, and immunohistochemical experiment reagent, analyze expression of the Shp2 albumen in liver cancer tissue, instruct liver cancer
Postoperative Sorafenib medication or the curative effect of assessment Sorafenib.
Described Shp2 polyclonal antibodies are that applicant place seminar is utilized after Shp2 recombinant protein immune rabbits voluntarily
Prepare, (referring to document Yokoyama, W.M., Christensen, M., Santos, G.D., et al.Production of
Monoclonal Antibodies.Current Protocols in Immunology.2006；74：2.5.1-2.5.25)
Described SABC reagent includes dimethylbenzene, ethanol, 3%H2O2Solution, 1%BSA confining liquids, DAB colour developing examinations
The goat anti-rabbit igg of agent, haematoxylin and horseradish peroxidase-labeled.
A second aspect of the present invention, there is provided Shp2 albumen judges Hepatectomy patient for Sorafenib sensitiveness in preparation
Reagent or kit in application.The postoperative hepatocarcinoma patient of Shp2 low expressions is sensitive to Sorafenib treatment in liver cancer tissue.
A third aspect of the present invention, there is provided Shp2 albumen instructs the reagent of Hepatectomy patient Sorafenib medication preparing
Or the application in kit.The postoperative hepatocarcinoma patient of Shp2 low expressions is suitable to be treated with Sorafenib in liver cancer tissue.
A fourth aspect of the present invention, there is provided Shp2 albumen judges the postoperative prognosis for taking Sorafenib liver cancer patient in preparation
Reagent or kit in application.The postoperative hepatocarcinoma patient Sorafenib of Shp2 low expressions treats its prognosis in liver cancer tissue
More preferably, the Sorafenib of whether taking of the high expression of Shp2 has no effect on patient's prognosis.
A fifth aspect of the present invention, there is provided a kind of method of the postoperative prognosis for taking Sorafenib liver cancer patient of judgement, institute
The method stated is the expression for detecting Shp2 albumen in liver cancer tissue.The postoperative hepatocarcinoma patient Sorafenib of Shp2 low expressions
Treat its prognosis more preferably, the Sorafenib of whether taking of the high expression of Shp2 has no effect on patient's prognosis.
The method of expression of the described detection Shp2 albumen in liver cancer tissue, comprises the following steps：
A () utilizes SABC reagent dimethylbenzene, ethanol, 3%H2O2Solution, 1%BSA confining liquids, DAB colour reagents, Soviet Union
Liver cancer tissue section is carried out immunohistochemical staining by the goat anti-rabbit igg of lignin and horseradish peroxidase-labeled；
B () is shot for digital photograph using microscope and imaging device；
C () provides scoring according to the artificial point system of immunohistochemical staining result.
Preferably, described method is comprised the following steps that：
(1) liver cancer tissue paraffin section is prepared, 60 DEG C of baking boxs are overnight；
(2) dewaxing of cutting into slices is to water；
(dimethylbenzene I 1. 10min → dimethylbenzene II 2. 10min → dimethylbenzene III 3. 10min → 100% ethanol 5min →
95% ethanol 5min → 85% ethanol 5min → 75% ethanol 5min → distilled water 5min)
(3) 3%H2O2Solution, room temperature places 20min；
(4) distilled water washes 5min × 3；
(5) antigen retrieval：Section is put into 0.01M citrate buffers (pH 6.0) boils 30min；
(6) room temperature is naturally cooled to, distilled water washes 5min × 3；
(7) 1%BSA closings 30min, 37 DEG C；
(8) get rid of deblocking liquid, do not wash, it is anti-directly Jia one, described one resist for rabbit Shp2 polyclonal antibodies (recognizable people,
Shp2 albumen in the mammals such as mouse), voluntarily prepare, dilution ratio 1: 75；Insert 30min in wet box, 37 DEG C, then 4 DEG C of ice
Case overnight 16 hours；
(9) 4 DEG C are taken out, room temperature rewarming 15min, and then 0.01M PBS wash 5min × 4；
(10) be added dropwise it is two anti-(horseradish peroxidase-labeled goat anti-rabbit igg, purchased from DAKO companies of Denmark, instant, without the need for
Dilution) 45min, 37 DEG C；
(11) 0.01M PBS wash 5min × 4, DAB colour developing 2-10min, Microscopic observation；
(12) distilled water color development stopping, haematoxylin redyes 10 seconds；
(13) running water returns indigo plant, distilled water immersion after breaking up；
(14) it is dehydrated transparent, cover glass covering；
(15) basis of microscopic observation positive staining, randomly selects 3 visuals field and takes pictures in liver cancer tissue；
(16) tissue samples are scanned using Image Scope (Aperio companies) software, it is soft using this after scanning
Algorithms (the Positive Pixel Count) program of part carries out " positive Pixel " calculating to each sample, is counted
Count according to such as following table：
Each tissue group score calculation method be Log10 [255/Iavg], wherein Iavg=(Iwp+Ip+Isp)/
(Nwp+Np+Nsp), i.e., positive mean intensity, computational methods：
Positive mean intensity=(weakly positive pixel overall strength+positive pixels overall strength+strong positive pixel overall strength)/(weak
Positive pixels quantity+positive pixels quantity+strong positive pixel number), the as SABC scoring of the tissue, for follow-up point
Analysis.
The high low expression standards of Shp2 are with the median of Shp2 expression scoring in 148 liver cancer tissues as boundary.
The Shp2 albumen of the present invention takes Sorafenib offer completely newly with being found to be after prediction Liver Cancer Operation for liver cancer correlation
Biological targets, to whether taking Sorafenib after Liver Cancer Operation there is important guiding to act on.Shp2 albumen low expressions it is postoperative
Hepatocarcinoma patient is sensitive to Sorafenib treatment, is suitable to be treated with Sorafenib, and prognosis is preferable after treating.
The present invention is taken pictures relative with Computer Image Processing software measure tumor tissues using immunohistochemistry technique, microscope
Shp2 albumen relative expression quantities in the tissue of knurl side, and with reference to Follow-up After information, after determining Shp2 expressing quantities and Liver Cancer Operation
There is correlation in the life cycle for taking Sorafenib patient, Shp2 albumen can be used for preparation and judge to take Sorafenib after Liver Cancer Operation
Biology target spot, Sorafenib is taken for hepatocarcinoma patient is postoperative there is important directive significance.For losing opportunity of operation
Liver cancer patient, it is possible to use puncture and obtain liver cancer tissue or the circulating tumor cell in collection blood samples of patients, carry out Shp2 tables
Up to horizontal detection, so as to assess its sensitiveness to Sorafenib.
Description of the drawings
Fig. 1 is Shp2 immunohistochemical staining results in 71 postoperative liver cancer tissues for not taking Sorafenib patient, can
See Shp2 expression height situation in tumor tissues.
Fig. 2 is that Shp2 takes immunohistochemical staining result in the liver cancer tissue of Sorafenib patient after 77 Liver Cancer Operations,
Shp2 expression height situation in visual tumors tissue.
Fig. 3 is the survival analysis figure that Sorafenib group and control group are taken in Shp2 low expression patients, it is seen that the low tables of Shp2
Medication group is compared with control group good prognosis up in patient.
Fig. 4 is the survival analysis figure that Sorafenib group and control group are taken in the high expression patients of Shp2, it is seen that the high tables of Shp2
Whether medication has no impact on prognosis to the patient for reaching.
Fig. 5 is sample 1Shp2 immunohistochemical staining result figures in liver cancer tissue, it is seen that Shp2 form and aspect in tumor tissues
To relatively by force, Follow-up results show that prognosis is poor after the clothes for patients Sorafenib.
Fig. 6 is sample 2Shp2 immunohistochemical staining result figures in liver cancer tissue, it is seen that Shp2 form and aspect in tumor tissues
To relatively by force, Follow-up results show that prognosis is poor after the clothes for patients Sorafenib.
Fig. 7 is sample 3Shp2 immunohistochemical staining result figures in liver cancer tissue, it is seen that Shp2 form and aspect in tumor tissues
To weaker, Follow-up results show that prognosis is preferable after the clothes for patients Sorafenib.
Fig. 8 is sample 4Shp2 immunohistochemical staining result figures in liver cancer tissue, it is seen that Shp2 form and aspect in tumor tissues
To weaker, Follow-up results show that prognosis is preferable after the clothes for patients Sorafenib.
Specific embodiment
The specific embodiment that the present invention is provided is elaborated with reference to embodiment.
Embodiment 1：
Collect 77 postoperative liver cancer tissues for taking Sorafenib patient and 71 postoperative are not taken Sorafenib patient's
Liver cancer tissue (liver cancer tissue is all from east hospital of liver and gall surgical department, and by 2 Pathologis hepatocellular carcinoma is diagnosed as), adopts and exempts from
Epidemic disease group method detects expression and Computation immunity groupization scoring of the Shp2 albumen in liver cancer tissue, comprises the following steps that：
(1) liver cancer tissue paraffin section is prepared, 60 DEG C of baking boxs are overnight；
(2) dewaxing of cutting into slices is to water；
(dimethylbenzene I 1. 10min → dimethylbenzene II 2. 10min → dimethylbenzene III 3. 10min → 100% ethanol 5min →
95% ethanol 5min → 85% ethanol 5min → 75% ethanol 5min → distilled water 5min)
(3) 3%H2O2Solution, room temperature places 20min；
(4) distilled water washes 5min × 3；
(5) antigen retrieval：Section is put into 0.01M citrate buffers (pH 6.0) boils 30min；
(6) room temperature is naturally cooled to, distilled water washes 5min × 3；
(7) 1%BSA closings 30min, 37 DEG C；
(8) get rid of deblocking liquid, do not wash, it is anti-directly Jia one, described one resist for rabbit Shp2 polyclonal antibodies (recognizable people,
Shp2 albumen in the mammals such as mouse), voluntarily prepare, dilution ratio 1: 75；Insert 30min in wet box, 37 DEG C, then 4 DEG C of ice
Case overnight 16 hours；
(9) 4 DEG C are taken out, room temperature rewarming 15min, and then 0.01M PBS wash 5min × 4；
(10) be added dropwise it is two anti-(horseradish peroxidase-labeled goat anti-rabbit igg, purchased from DAKO companies of Denmark, instant, without the need for
Dilution), 45min, 37 DEG C；
(11) 0.01M PBS wash 5min × 4, DAB colour developing 2-10min, Microscopic observation；
(12) distilled water color development stopping, haematoxylin redyes 10 seconds；
(13) running water returns indigo plant, distilled water immersion after breaking up；
(14) it is dehydrated transparent, cover glass covering；
(15) basis of microscopic observation positive staining, randomly selects 3 visuals field and takes pictures in liver cancer tissue；
(16) tissue samples are scanned using Image Scope (Aperio companies) software, it is soft using this after scanning
Algorithms (the Positive Pixel Count) program of part carries out " positive Pixel " calculating to each sample, is counted
Count according to such as following table：
Each tissue group score calculation method be Log10 [255/Iavg], wherein Iavg=(Iwp+Ip+Isp)/
(Nwp+Np+Nsp), i.e., positive mean intensity, computational methods：
Positive mean intensity=(weakly positive pixel overall strength+positive pixels overall strength+strong positive pixel overall strength)/(weak
Positive pixels quantity+positive pixels quantity+strong positive pixel number), the as SABC scoring of the tissue, for follow-up point
Analysis.
Suffered from 71 postoperative Sorafenibs of not taking using the experimental procedure detection Shp2 albumen of above ImmunohistochemistryMethods Methods
The Expression In Hepatocellular Carcinoma situation of person, and expression of tumor tissue level is determined according to Computer Image Processing software, according to expression
Patient is divided into high expression group and low expression group (see Fig. 1) by situation.The detection and analysis of relevant Shp2 expression may refer to applicant
Patent document (application of the .Shp2 such as Wang Hongyang albumen in prognosis in hcc assessment kit is prepared for having authorized：China, ZL
2013 1 0005628.6.[P].2013-04-24)
Embodiment 2：
Sorafenib patient postoperative is taken at 77 using the experimental procedure detection Shp2 albumen of above ImmunohistochemistryMethods Methods
Liver cancer tissue paraffin section in expression, and determine expression of tumor tissue level according to Computer Image Processing software,
Patient is divided into by high and low expression group (see Fig. 2) according to expression.
Embodiment 3：
Liver cancer patient carries out height packet according to Shp2 protein expressions situation, and data analysis adopts SPSS softwares 18.0, raw
Deposit tracing analysis and use Kaplan-Meier methods, compare between two groups of height and checked with log-rank.As a result the low tables of Shp2 are found
Up in patient, medication group has significant difference (P=0.041) compared with control group good prognosis, two groups of survival analysises.As a result point out：
The patient of Shp2 low expressions is good to Sorafenib reactivity, is adapted to Sorafenib treatment.See Fig. 3.
Embodiment 4：
With reference to prognosis information, survival analysis, data point are carried out to the high expression group of Shp2 albumen in medication group and non-medication group
Analysis adopts SPSS softwares 18.0, survivorship curve analysis to use Kaplan-Meier methods, compare between two groups and checked with log-rank.
As a result in finding the high expression patients of Shp2, the prognosis of medication group and control group does not have significant difference (P=0.713).As a result carry
Show：The patient of the high expression of Shp2 is poor to Sorafenib reactivity, is not suitable for Sorafenib treatment.See Fig. 4.
Embodiment 5：
Sample 1：The histotomy of certain patients with hepatocellular carcinoma tumour, is detected using the test procedure of above ImmunohistochemistryMethods Methods
Expression of the Shp2 albumen in liver cancer tissue.The displaing micro picture of liver cancer tissue is as shown in Figure 5.It is computed, the immunity of the tissue
Groupization scoring 0.42, higher than the median 0.36 that Shp2 is expressed in liver cancer.
Jing Follow-up Afters are known, start to take Sorafenib, Overall survival 9 months, Sulfurless fixative 5 after the operation in patients
Month, prognosis is poor.See Fig. 5.
Embodiment 6：
Sample 2：The histotomy of certain patients with hepatocellular carcinoma tumour, is detected using the test procedure of above ImmunohistochemistryMethods Methods
Expression of the Shp2 albumen in liver cancer tissue.The displaing micro picture of liver cancer tissue is as shown in Figure 6.It is computed, the immunity of the tissue
Groupization scoring 0.47, higher than 0.36.
Jing Follow-up Afters know, start to take Sorafenib after the operation in patients, Overall survival 12.5 months, and Sulfurless fixative is only
7 months, prognosis was poor.See Fig. 6.
Embodiment 7：
Sample 3：The histotomy of certain patients with hepatocellular carcinoma tumour, is detected using the test procedure of above ImmunohistochemistryMethods Methods
Expression of the Shp2 albumen in liver cancer tissue.The displaing micro picture of liver cancer tissue is as shown in Figure 7.It is computed, the immunity of the tissue
Groupization scoring 0.18, less than 0.36.
Jing Follow-up Afters know, Sorafenib is taken after the operation in patients, total life span more than 25 months, and postoperative 25
The moon finds no transfer and relapse, and prognosis is preferable.See Fig. 7.
Embodiment 8：
Sample 4：The histotomy of certain patients with hepatocellular carcinoma tumour, is detected using the test procedure of above ImmunohistochemistryMethods Methods
Expression of the Shp2 albumen in liver cancer tissue.The displaing micro picture of liver cancer tissue is as shown in Figure 8.It is computed, the immunity of the tissue
Groupization scoring 0.13, less than 0.36.
Jing Follow-up Afters know that Sorafenib is taken after the operation in patients, and total life span is more than 29.5 months and postoperative
Transfer and relapse is found no within 29.5 months, prognosis is preferable.See Fig. 8.
From above result of the test, detect that Shp2 protein moleculars expression can be instructed by the method using SABC
Sorafenib postoperative.When immunohistochemical staining is the liver cancer patient of Shp2 low expressions, its is postoperative to take Sorafenib effect
More preferably.Obviously, the expression of Shp2 albumen has correlation with the postoperative prognosis for taking Sorafenib liver cancer patient, therefore, with
Used as molecular target, carrying out detection to its expression can instruct Sorafenib postoperative to Shp2 albumen.Accordingly, specificity is anti-
The antibody of Shp2 albumen, including monoclonal antibody and polyclonal antibody, can be used to prepare judge whether take Suo La after Liver Cancer Operation
The reagent or kit of luxuriant and rich with fragrance Buddhist nun, this it will be apparent to those skilled in the art that.
General principle, principal character and the advantages of the present invention of the present invention has been shown and described above.The technology of the industry
Personnel it should be appreciated that the present invention is not restricted to the described embodiments, the simply explanation described in above-described embodiment and specification this
The principle of invention, of the invention without departing from the spirit and scope of the present invention also to have various changes and modifications, these changes
Change and improvement is both fallen within scope of the claimed invention.The claimed scope of the invention by appending claims and its
Equivalent is defined.
Claims (4)
1.Shp2 albumen is preparing liver cancer to the application in Sorafenib curative effect evaluation kit.
2. Shp2 albumen according to claim 1 prepare liver cancer to the application in Sorafenib curative effect evaluation kit,
Characterized in that, the application is referred to Shp2 albumen as molecular labeling, using Shp2 monoclonal antibodies or polyclonal antibody, knot
Immunohistochemical kit is closed, expression of the Shp2 albumen in liver cancer tissue is detected, according to Shp2 albumen in liver cancer tissue
Expression assesses curative effect of the liver cancer patient to Sorafenib.
3. Shp2 albumen according to claim 2 is in liver cancer to the application in Sorafenib curative effect evaluation kit, and it is special
Levy and be, the application is to detect expression of the Shp2 albumen in liver cancer tissue in vitro using described kit, its detection
Method is comprised the following steps：
A liver cancer tissue section is carried out immunohistochemical staining by ()；
B () is shot for digital photograph using microscope and imaging device；
C () processes software analysis tumor tissues positive signal intensity using biometric image, provide scoring；
D () is according to Shp2 protein moleculars relative expression quantity in score calculation tumor tissues.
4. Shp2 albumen according to claim 3 in liver cancer patient is prepared to Sorafenib curative effect evaluation kit should
With, it is characterised in that when SABC scoring is the high expression of Shp2 albumen higher than 0.36, patient is insensitive to Sorafenib；When
Scoring is Shp2 albumen low expressions less than 0.36, and patient is sensitive to Sorafenib.
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| CN114167061A (en) * | 2020-09-10 | 2022-03-11 | 中国人民解放军海军军医大学 | Application of FOXA3 protein in preparation of kit for liver cancer prognosis evaluation and sorafenib curative effect prediction |
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