CN102445543B - Reagent for auxiliary diagnosing lung cancer lymph node metastasis - Google Patents
Reagent for auxiliary diagnosing lung cancer lymph node metastasis Download PDFInfo
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Abstract
The invention discloses a reagent for auxiliarily diagnosing lung cancer lymph node metastasis, comprising 8 antibodies which are used for detecting 8 protein markers which are MMP1 (matrix metalloproteinase-1), TIMP1 (tissue inhibitor of metalloproteinases metallopeptidase inhibitor 1), IQGAP1 (IQ motif containing GTPase activating protein 1), TPX2 (targeting protein for Xklp2), uPA (Urokinase-type plasminogen activator), Cathepsin-D, Fascin and pIgR/SC (polymeric immunoglobulin receptor/secretory component). By adopting the 8 antibodies and an immunohistochemical staining result, lung cancer lymph node metastasis can be auxiliarily diagnosed, and the reagent is expected to be used for the risk estimation of lung squamous cell cancer lymph node metastasis and the prognostic prediction. The reagent has high creditability, strong practicability and clinical use value based on the clinical routine immunohistochemical staining technology when the reagent is used for auxiliary diagnosis.
Description
Technical field
The present invention relates to the reagent of a kind of auxiliary diagnosis lung cancer lymphatic metastasis.
Background technology
Tumour has become one of major disease of serious threat human survival health, and its incidence of disease and mortality ratio are all ascendant trend year by year, and the annual new cases of lung cancer and death toll all occupy various malignant tumours prostatitis.Research shows, there is 90% lung squamous cancer patient to die from the transfer of tumour, this is because lung cancer is without clear and definite sentinel lymph node to a certain extent, in surgical procedure, be confined to the restriction of lymph node dissection scope, the micro metastasis that may exist potential light microscopic to detect, finally causes diagnosing lymph node metastatsis difficulty and then affects the formulation of therapeutic scheme and patient's survival rate.Therefore, utilize molecular marked compound to assist clinical diagnosis, significant to the raising of the diagnosis and treatment of lung cancer patient and survival rate undoubtedly.
The appearance of high-throughput techniques (as biochip technology), has promoted the screening of tumor molecular marker greatly.Based on these technology, emerge a collection of molecular marked compound for diagnosing tumor and prognosis prediction.But these methods are the detection based on DNA, RNA demeanour all.And these biomacromolecules are all positioned at central dogma upstream, and the direct executor of NOT-function.And its detection method is not yet universal in clinical diagnosis, larger with clinical disconnection, and practicality is not high.
Summary of the invention
The reagent that the object of this invention is to provide the lymphatic metastasis of a kind of auxiliary diagnosis lung cancer.
The invention provides a kind of reagent, comprise following seven kinds of antibody: anti-MMP1 antibody, anti-TIMP1 antibody, anti-IQGAP1 antibody, anti-CTSD antibody, anti-TPX2 antibody, anti-uPA antibody and anti-FSCN1 antibody, described reagent can be used for the lymphatic metastasis of auxiliary diagnosis lung cancer and/or auxiliary assessment lung cancer lymphatic metastasis risk.
Described reagent also can comprise the 8th kind of antibody, i.e. anti-pIgR/SC antibody.
Described reagent specifically can be comprised of described anti-MMP1 antibody, described anti-TIMP1 antibody, described anti-IQGAP1 antibody, described anti-CTSD antibody, described anti-TPX2 antibody, described anti-uPA antibody, described anti-FSCN1 antibody and described anti-pIgR/SC antibody.
Every kind of described antibody is all packed separately.
Every kind of described antibody all can be the polyclonal antibody of monoclonal antibody or commercial sources acquisition.
Described anti-MMP1 antibody specific can be the antibody that catalog number that Oncogene produces is MS-802-P; Described anti-TIMP1 antibody specific can be the antibody that catalog number that Santa Cruz produces is sc-21734; Described anti-IQGAP1 antibody specific can be the antibody that catalog number that BD Biosciences produces is 610612; Described anti-CTSD antibody specific can be the antibody that catalog number that Santa Cruz produces is sc-10725; Described anti-TPX2 antibody specific can be the antibody that catalog number that Biolegene produces is 628002; Described anti-uPA antibody specific can be the antibody that catalog number that Calbiochem produces is 1M13L; Described anti-FSCN1 antibody specific can be the antibody that catalog number that Santa Cruz produces is sc-21743; Described anti-pIgR/SC antibody specific can be the antibody that catalog number that DAKO produces is A0187.
Described reagent can be used for preparing the kit of the lymphatic metastasis of auxiliary diagnosis lung cancer and/or auxiliary assessment lung cancer lymphatic metastasis risk.The present invention also protects the kit that comprises described reagent, and described kit can be used for the lymphatic metastasis of auxiliary diagnosis lung cancer and/or auxiliary assessment lung cancer lymphatic metastasis risk.
For sample to be tested (patient's to be measured histotomy), can with 8 antibody, carry out SABC respectively, obtain the appraisal result of 8 antigens, then diagnose or assess according to the appraisal result of each antigen.The advantage of this method is the disposable appraisal result that obtains all antigens, save time, but partial evaluation result is not applied.
For sample to be tested (patient's to be measured histotomy), also can by different antibodies, carry out SABC successively by the order shown in Fig. 1, according to the appraisal result of antigen, carry out next step successively, finally obtain diagnostic result or assessment result.The advantage of this method is only to adopt successively partial antibody can be diagnosed or assessment result, save the consumption of antibody, but required time is longer.
Reagent provided by the invention comprises 8 kinds of antibody for detection of 8 protein markers (MMP1, TIMP1, IQGAP1, TPX2, uPA, Cathepsin-D, Fascin and pIgR/SC).Apply 8 kinds of antibody, by immunohistochemical staining result, can the lymphatic metastasis of auxiliary diagnosis lung cancer, be expected to be applied to lung squamous cancer lymphatic metastasis risk assessment and prognosis prediction.While applying reagent auxiliary diagnosis of the present invention, based on routine clinical expression, have higher credible in, there is stronger practicality and clinical use value.
Applying kit of the present invention detects, tool has the following advantages: (1) is in whole diagnostic procedure, each Nodes is all only tested to the SABC appraisal result of single protein, completely independent between different nodes (protein marker), therefore avoided incomparable problem between the scoring of different proteins SABC; (2) the primary tumor tumor tissues based on excision dyes, and has avoided the problem of lymph node dissection scope in operation, consistent with the diagnosis material therefor of clinical disease natural sciences routine again, has increased greatly the availability in clinical; (3) executor-protein expression level based on based on biological function, more accurate.
Accompanying drawing explanation
Fig. 1 is the process flow diagram of the reagent auxiliary diagnosis lymphatic metastasis of 52 routine From Lung Squamous Carcinoma Patients Application Examples 2; The circular protein molecular label representing for dividing into groups in figure, the conspicuousness of two group differences when its inside comprises protein title and differentiates grouping according to this albumen; Rounded lower portion is the SABC scoring judging; The case that meets this judgment criteria enters the check of corresponding protein expression below according to line direction; In figure, bottommost is " terminal " of grouping; HR represents lymphatic metastasis, and LR represents that lymph node does not shift.
Embodiment
Following embodiment is convenient to understand better the present invention, but does not limit the present invention.Experimental technique in following embodiment, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.Quantitative test in following examples, all arranges and repeats experiment, results averaged for three times.
The performance history of embodiment 1, reagent
Training set (training set) comprises 255 routine lung cancer cases.First build a set of cancerous lung tissue microarray, utilized the organization chip that wherein comprises lung squamous cancer, completed the immunohistochemical staining and the interpretation of result that amount to 23 candidate's lung cancer correlating markings albumen.On this basis, the expression situation in 319 routine lung squamous cancer primary tumor tissues and the relation of lymphatic metastasis are studied for above-mentioned 23 candidate's marker proteins to adopt generalized linear regression model (Generalized Linear Model, GLM).Result shows, has 9 expressions and lymphatic metastasis significant correlation (p < 0.05) in 23 albumen.Wherein TIMP1, MMP1, TPX2, Aurora-A, uPA, Osteopontin and Cathepsin-D and lymphatic metastasis correlation---they express stronger in primary tumor, the carry down risk of moving of tumor lympha occur higher; The expression of nm23-H1 and 14-3-3 with lymphatic metastasis negative correlation.
According to the result of calculation of above-mentioned generalized linear regression model, by the SABC scoring " recodification " of 23 albumen.That is, all GLM models think to have the albumen of negative correlativing relation with lymphatic metastasis, and its immunohistochemistry score value is multiplied by " 1 " becomes negative value; And remain unchanged with its SABC of albumen scoring that lymphatic metastasis has a positive correlation.So the SABC of " recodification " scoring conduct " input " is for the structure of next step mathematical model.Its symbol of data after " recodification " has directly reflected the relation of protein expression and lymphatic metastasis (or lymphatic metastasis risk) like this, contributes to the later stage to build decision-tree model and diagnoses (or risk profile).
Consider that different (Partial Protein is positioned nucleus for the celluar localization of different proteins, another Partial Protein is positioned in cytoplasm), dye antibody used tire and Color also differs widely, therefore different protein immunization group appraisal result do not have comparability.Simultaneously, the data pre-service and the statistical method that in the existing molecular marked compound research based on biochip, adopt, as support vector machine (Supported Vector Machine, SVM), k nearest neighbor method (K Nearest Neighborhood, KNN) etc. all requires between handled different genes/probe comparable.Therefore to the immunohistochemical staining score data of different proteins, use these common molecule parting methods by the result directly leading to errors.For the feature of such one group of data, in methodology, select to adopt " recurrence is cut apart decision tree " (Recursive Partitioning Decision Tree) algorithm to set up lung cancer diagnosing lymph node metastatsis model (or forecast model).In the decision-tree model of setting up in the method, the SABC score information self-decision tree upper end (root) of every routine case enters model, the SABC scoring of the single protein marker of it being indicated at each Nodes is tested, and select to enter next stage checkout procedure and continue to judge according to decision criteria according to decision criteria, until arrive this tree shaped model " terminal " bottom, and obtain the diagnosing lymph node metastatsis result (or risk profile result) based on this model.
To utilize diagnosing lymph node metastatsis result and the postoperative histopathologic diagnosis result of lung cancer case of above-mentioned recurrence cut tree Model checking to compare, find that its accuracy in " training set " is 78.0%, sensitivity and specificity is respectively 83.0% and 70.3%.
The composition of embodiment 2, reagent
Reagent is comprised of eight kinds of antibody of independent packaging; Eight kinds of antibody are to buy and obtain, specific as follows:
Anti-MMP1 antibody: Oncogene produces, and catalog number is MS-802-P, and working concentration is 1: 300.
Anti-TIMP1 antibody: Santa Cruz produces, and catalog number is sc-21734, and working concentration is 1: 50.
Anti-IQGAP1 antibody: BD Biosciences produces, and catalog number is 610612, and working concentration is 1: 100.
Anti-CTSD antibody: Santa Cruz produces, and catalog number is sc-10725, and working concentration is 1: 100.
Anti-TPX2 antibody: Biolegene produces, and catalog number is 628002, and working concentration is 1: 500.
Anti-uPA antibody: Calbiochem produces, and catalog number is 1M13L, and working concentration is 1: 100.
Anti-pIgR/SC antibody: DAKO produces, and catalog number is A0187, and working concentration is 1: 300.
Anti-FSCN1 antibody: Santa Cruz produces, and catalog number is sc-21743, and working concentration is 1: 100.
This reagent is applied to detect following eight kinds of antigens (protein marker):
Endochylema antigen: MMP1, TIMP1, IQGAP1, uPA, CTSD (Cathepsin-D), FSCN1 (Fascin) and pIgR/SC; Cell nuclear antigen: TPX2.
MMP1 (Chinese is matrix metallopeptidase 1, and English name is matrix metallopeptidase 1, Swiss-Prot ACCESSION NO.P03956).TIMP1 (Chinese is TIMP1, and English name is tissue inhibitor of metalloproteinase 1, Swiss-Prot ACCESSION NO.P01033).IQGAP1 (Chinese is the gtpase activating protein 1 containing IQ motif, and English name is IQ motif containing GTPase activating protein 1, Swiss-Prot ACCESSION NO.P46940).UPA (Chinese is UPA, and English name is plasminogen activator, urokinase, Swiss-Prot ACCESSION NO.P00749).CTSD (Chinese is cathepsin D, and English name is cathepsin D, Swiss-Prot ACCESSION NO.P07339).FSCN1 (Chinese is fascin homolog 1, and English name is fascin homolog 1, Swiss-Prot ACCESSION NO.Q16658).PIgR/SC (Chinese is polymeric immunoglobulin receptor secretory piece, and English name is polymeric immunoglobulin receptor/secretory component, Swiss-Prot ACCESSION NO.P01833).TPX2 (Chinese is microtubule-associated protein homolog, and English name is microtubule-associated, homolog, Swiss-Prot ACCESSION NO.Q9ULWO).
The application of embodiment 3, reagent
52 routine From Lung Squamous Carcinoma Patients (volunteer of informed consent), for there is the patient of lymphatic metastasis in 24 examples wherein, and for there is not the patient of lymphatic metastasis in 28 examples.With the reagent of embodiment 2,52 routine From Lung Squamous Carcinoma Patients are carried out to SABC (each patient carries out SABC with eight kinds of antibody in reagent respectively, and the experiment material of SABC is the section of the primary tumor tumor tissues of corrective surgery excision).
According to ImmunohistochemistryResults Results, for each antigen, mark.The SABC standards of grading of endochylema antigen: the qualitative integration+cell dyeing of cell dyeing intensity area quantitative integration=appraisal result; The qualitative integration of cell dyeing intensity is: do not dye=0, slight dyeing=1, moderate dyeing=2, strong dyeing=3; Cell dyeing area quantitative integration is: acellular dyeing=0, < 25% cell dyeing=1,25%～50% cell dyeing=2, > 50% cell dyeing=3.The SABC standards of grading of cell nuclear antigen: obviously nucleus is colored as the positive, the number percent of numeration positive cell number, non-coloring is decided to be 0; Positive cell number≤10% is decided to be 1; 11%-30% is decided to be 2; 31%-50% is decided to be 3; > 50% is decided to be 4.
According to appraisal result, each patient is carried out to lymphatic metastasis auxiliary diagnosis, diagnostic criteria is as follows:
MMP1 appraisal result be greater than 1, IQGAP1 appraisal result be greater than 1 for lymphatic metastasis patient; MMP1 appraisal result be greater than 1, IQGAP1 appraisal result be less than or equal to 1, FSCN1 appraisal result be less than or equal to-2 for lymphatic metastasis patient; MMP1 appraisal result be greater than 1, IQGAP1 appraisal result be less than or equal to 1, FSCN1 appraisal result be greater than-2 for lymphatic metastasis patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be greater than 1, TPX2 appraisal result be less than or equal to 1 for lymph node, do not shift patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be greater than 1, TPX2 appraisal result be greater than 1 for lymphatic metastasis patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be less than or equal to 0 for lymph node, do not shift patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be greater than 0, uPA appraisal result be less than or equal to 0, pIgR/SC appraisal result be less than or equal to-2 for lymph node, do not shift patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be greater than 0, uPA appraisal result be less than or equal to 0, pIgR/SC appraisal result be greater than-2 for lymph node, do not shift patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be greater than 0, uPA appraisal result be greater than 0, TPX2 be greater than 2 for lymphatic metastasis patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be greater than 0, uPA appraisal result be greater than 0, TPX2 appraisal result be less than or equal to 2, FSCN1 appraisal result be less than or equal to-2 for lymph node, do not shift patient; MMP1 appraisal result be less than or equal to 1, TIMP1 appraisal result be less than or equal to 1, CTSD appraisal result be greater than 0, uPA appraisal result be greater than 0, TPX2 appraisal result be less than or equal to 2, FSCN1 appraisal result be greater than-2 for lymphatic metastasis patient.
The concrete outcome of 52 routine From Lung Squamous Carcinoma Patients is in Table 1.
The concrete outcome of the routine From Lung Squamous Carcinoma Patients of table 152 (LR representative is not shifted, and HR represents transfer)
The accuracy of diagnosing with the reagent of embodiment 2 (ratio of actual lymphatic metastasis in the patient who is lymphatic metastasis with the reagent diagnosis of embodiment 2) is 82.7%, susceptibility (be lymphatic metastasis with the reagent diagnosis of embodiment 2 in the patient of actual lymphatic metastasis ratio) is 79.2%, specificity (being that the ratio that the reagent diagnosis lymph node with embodiment 2 does not shift does not occur in the patient of lymphatic metastasis reality) is 85.7%, close with the result obtaining in " training set ", show to adopt reagent of the present invention, according to above-mentioned standard, lymphatic metastasis is carried out to auxiliary diagnosis and there is higher reliability.
During by the lung cancer lymphatic metastasis risk of the reagent assess patient of embodiment 2, the same said method that adopts, only, when assessment, the lymphatic metastasis patient in above-mentioned diagnosis is lymphatic metastasis high-risk patient, and it is lymphatic metastasis low-risk patient that the lymph node in above-mentioned diagnosis does not shift patient.
Embodiment 4, Application Example 2 are carried out the other method of auxiliary diagnosis
52 routine From Lung Squamous Carcinoma Patients in embodiment 3 also can carry out SABC by different antibodies successively by the order shown in Fig. 1, carry out next step (standards of grading are with embodiment 3) successively according to the appraisal result of antigen, specific as follows:
First carry out SABC I, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 1 carry out SABC II; Appraisal result be greater than 1 carry out SABC III;
SABC II, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 1 carry out SABC IV; Appraisal result be greater than 1 carry out SABC V;
SABC IV, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 0 for lymph node, do not shift patient; Appraisal result be greater than 0 carry out SABC VI;
SABC VI, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 0 carry out SABC VII; Appraisal result be greater than 0 carry out SABC VIII;
SABC VII, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to-2 for lymph node, do not shift patient; Appraisal result be greater than-2 for lymph node, do not shift patient;
SABC VIII, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 2 carry out SABC IX; Appraisal result be greater than 2 for lymphatic metastasis patient;
SABC IX, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to-2 for lymph node, do not shift patient; Appraisal result be greater than-2 for lymphatic metastasis patient;
SABC V, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 1 for lymph node, do not shift patient; Appraisal result be greater than 1 for lymphatic metastasis patient;
SABC III, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to 1 carry out SABC X; Appraisal result be greater than 1 for lymphatic metastasis patient;
SABC X, ImmunohistochemistryResults Results is marked; Appraisal result be less than or equal to-2 for lymphatic metastasis patient; Appraisal result be greater than-2 for lymphatic metastasis patient;
In SABC I, primary antibodie is anti-MMP1 antibody; In SABC II, primary antibodie is anti-TIMP1 antibody; In SABC III, primary antibodie is anti-IQGAP1 antibody; In SABC IV, primary antibodie is anti-CTSD antibody; In SABC V, primary antibodie is anti-TPX2 antibody; In SABC VI, primary antibodie is anti-uPA antibody; In SABC VII, primary antibodie is anti-pIgR/SC antibody; In SABC VIII, primary antibodie is anti-TPX2 antibody; In SABC IX, primary antibodie is anti-FSCN1 antibody; In SABC X, primary antibodie is anti-FSCN1 antibody.
During by the lung cancer lymphatic metastasis risk of the reagent assess patient of embodiment 2, the same said method that adopts, only, when assessment, the lymphatic metastasis patient in above-mentioned diagnosis is lymphatic metastasis high-risk patient, and it is lymphatic metastasis low-risk patient that the lymph node in above-mentioned diagnosis does not shift patient.
Claims (6)
1. the reagent of auxiliary diagnosis lung cancer lymphatic metastasis, comprises following seven kinds of antibody: anti-MMP1 antibody, anti-TIMP1 antibody, anti-IQGAP1 antibody, anti-CTSD antibody, anti-TPX2 antibody, anti-uPA antibody and anti-FSCN1 antibody.
2. reagent as claimed in claim 1, is characterized in that: described reagent also comprises anti-pIgR/SC antibody.
3. reagent as claimed in claim 2, is characterized in that: described reagent is comprised of described anti-MMP1 antibody, described anti-TIMP1 antibody, described anti-IQGAP1 antibody, described anti-CTSD antibody, described anti-TPX2 antibody, described anti-uPA antibody, described anti-FSCN1 antibody and described anti-pIgR/SC antibody.
4. as the reagent as described in arbitrary in claims 1 to 3, it is characterized in that: every kind of described antibody is packing separately all; Every kind of described antibody is the polyclonal antibody of monoclonal antibody or commercial sources acquisition.
5. the application of arbitrary described reagent in the kit of preparing the lymphatic metastasis of auxiliary diagnosis lung cancer in claim 1 to 4.
6. the kit of auxiliary diagnosis lung cancer lymphatic metastasis, comprises arbitrary described reagent in claim 1 to 4.
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| CN201010299919.7A CN102445543B (en) | 2010-10-08 | 2010-10-08 | Reagent for auxiliary diagnosing lung cancer lymph node metastasis |
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| CN201010299919.7A CN102445543B (en) | 2010-10-08 | 2010-10-08 | Reagent for auxiliary diagnosing lung cancer lymph node metastasis |
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| CN102445543B true CN102445543B (en) | 2014-03-12 |
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| CN105734146B (en) * | 2016-03-31 | 2019-11-12 | 北京博奥医学检验所有限公司 | A kind of molecular marker of diagnosis and treatment lung squamous cancer transfer |
| CN107589263B (en) * | 2017-11-02 | 2019-01-25 | 武汉迈特维尔生物科技有限公司 | A kind of small molecule marker indicating lung cancer lymphatic metastasis and the application in terms of diagnosis |
| US20230192888A1 (en) * | 2020-02-27 | 2023-06-22 | S&T Biomed Co., Ltd. | Monoclonal antibody of matrix metalloproteinase-1, detection kit and detection method thereof |
| CN112921087A (en) * | 2021-02-03 | 2021-06-08 | 复旦大学附属金山医院(上海市金山区核化伤害应急救治中心、上海市金山区眼病防治所) | Application of CTSD (cytotoxic T lymphocyte) as diagnosis marker in construction of lung squamous cell carcinoma prognosis prediction model |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070037224A1 (en) * | 2005-08-11 | 2007-02-15 | Hamer Peter J | Quantitative assays for PDGFR-beta in body fluids |
| US20100047771A1 (en) * | 2005-01-31 | 2010-02-25 | Jeong Ho Yoon | Markers for the diagnosis of lung cancer |
-
2010
- 2010-10-08 CN CN201010299919.7A patent/CN102445543B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100047771A1 (en) * | 2005-01-31 | 2010-02-25 | Jeong Ho Yoon | Markers for the diagnosis of lung cancer |
| US20070037224A1 (en) * | 2005-08-11 | 2007-02-15 | Hamer Peter J | Quantitative assays for PDGFR-beta in body fluids |
Non-Patent Citations (4)
| Title |
|---|
| An Approach to Studying Lung Cancer-related Proteins in Human Blood;Ting Xiao;《Molecula r& Cellular Proteomics》;20050620;第4卷(第10期);第1480-1486页 * |
| 利用组织芯片筛选肺鳞癌转移相关分子的初步研究;林冬梅;《中华医学会病理学分会2007年学术年会暨第九届全国病理大会论文汇编》;20071231;第148页 * |
| 肖汀.多聚免疫球蛋白受体(pIgR/SC)在肺癌组织的表达及其临床意义.《癌变 畸变 突变》.2008,第20卷(第3期),第0182-0187页. * |
| 肺癌淋巴结转移标志物研究进展;刘懿;《中国肺癌杂志》;20090531;第12卷(第5期);第440-447页 * |
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