WO2021213261A1 - Kit et méthode de détection permettant de détecter des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique - Google Patents

Kit et méthode de détection permettant de détecter des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique Download PDF

Info

Publication number
WO2021213261A1
WO2021213261A1 PCT/CN2021/087719 CN2021087719W WO2021213261A1 WO 2021213261 A1 WO2021213261 A1 WO 2021213261A1 CN 2021087719 W CN2021087719 W CN 2021087719W WO 2021213261 A1 WO2021213261 A1 WO 2021213261A1
Authority
WO
WIPO (PCT)
Prior art keywords
peripheral blood
add
gastric cancer
ctc
solution
Prior art date
Application number
PCT/CN2021/087719
Other languages
English (en)
Chinese (zh)
Inventor
夏梅
高德海
李胜
李�浩
Original Assignee
山东第一医科大学(山东省医学科学院)
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 山东第一医科大学(山东省医学科学院) filed Critical 山东第一医科大学(山东省医学科学院)
Publication of WO2021213261A1 publication Critical patent/WO2021213261A1/fr

Links

Images

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
    • G01N33/57484—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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0693—Tumour cells; Cancer cells
    • C12N5/0694—Cells of blood, e.g. leukemia cells, myeloma cells
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
    • C12N2509/10—Mechanical dissociation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70532—B7 molecules, e.g. CD80, CD86

Definitions

  • the invention provides a kit and a detection method for detecting the PD-L1 gene mutation of a patient through peripheral blood circulating tumor cells and gastric cancer, and belongs to the technical field of molecular biology.
  • Gastric cancer is a highly fatal malignant tumor with the fourth highest incidence in the world (950,000 new cases per year) and the third highest among cancer-related deaths in 2012.
  • the 5-year survival rate of gastric cancer patients is less than 30%, and about 50% of gastric cancer patients suffer tumor recurrence or metastasis after curative resection. Tumor recurrence and metastasis are the main causes of death in patients with gastric cancer.
  • Circulating tumor cells are tumor cells that fall off from solid tumors and enter the peripheral blood circulation. Since they were discovered in 1989, there have been a variety of methods for detecting circulating tumor cells in the peripheral blood. Recent studies have shown that its detection has important clinical significance for evaluating the prognosis of cancer patients, especially advanced cancer patients, and selecting appropriate individualized treatments. Because CTC detection has the characteristics of minimally invasive and real-time detection, it is called "liquid biopsy" of tumors.
  • the immunotherapy with PD-1/PD-L1 as an immune target has brought a new light to the treatment of gastric cancer.
  • immune suppression is closely related to immune escape and the overexpression of PD-L1 in tumor cells.
  • Tumor cells can bind to PD-1 on the surface of immune cells and T cells through PD-L1 on their surface, and conduct inhibitory signals to make T cells
  • the inability to recognize tumor cells and send out attack signals to tumor cells leads to immune escape of tumor cells.
  • CTC circulating tumor cells
  • the efficacy of PD-1 or PD-L1 immune preparations is mostly related to the immunohistochemical expression level of PD-L1 in tumor tissues, suggesting that the expression level of PD-L1 may be a biomarker for predicting the efficacy of PD-1 immunotherapy; there are also studies It shows that the high expression of PD-L1 in gastric cancer tissue is positively correlated with tumor aggressiveness.
  • CTC circulating tumor cell
  • Shandong First Medical University, Shandong Pharmaceutical Research Institute and Shandong Qixin Biotechnology Co., Ltd., Shandong Yuxiao Biotechnology Co., Ltd., Jinan Xingen Biotechnology Co., Ltd., Shandong Discovery Biotechnology Co., Ltd. and other units have Research on the industrialization of key technologies for tumor cell detection and identification.
  • This project is a major scientific and technological innovation project in Shandong Province. This project will take the Shandong Provincial Pharmaceutical Research Institute on the Jinan Campus of Shandong First Medical University as the core and implement the registrant system.
  • Circulating tumor cell detection and identification of core diagnostic technology, and further registration and identification of diagnostic kits to include PD1, PD-L1, ER, PR, Her-2, GPC-3, VEGF, P53, Vimentin, TKI-EGFR, RAS, CK, ALK-D5F3, CD20, ALK/EML4, Beta-catenin, E-Cadherin, EP-CAM, HPV, IDH-1, PSA, PSMA, VEGF, GFAP, cytokeratin, AE1/AE3, estrogen receptor, pregnancy Hormone receptors, BCA-225, CA125, CEA, EMA, ERCC1, HPV, Ki-67, P53, TOP2A, etc.
  • the identification and diagnosis kits are industrialized and promoted through cooperation with Shandong Qixin Biotechnology Co., Ltd., Shandong Yuxiao Biotechnology Co., Ltd., Jinan Xingen Biotechnology Co., Ltd., and Shandong Discovery Biotechnology Co., Ltd., which are registered in Jinan.
  • the present invention provides a method for detecting PD-L1 gene mutations in peripheral blood circulating tumor cells of gastric cancer patients for non-diagnostic purposes : Use a membrane filtration device to separate and obtain CTCs in the peripheral blood of patients with advanced or recurrent gastric cancer who cannot obtain tissue specimens, and further use immunohistochemistry to detect the expression of CTC's PD-L1.
  • a kit for detecting PD-L1 gene mutations in circulating tumor cells in the peripheral blood of patients with gastric cancer including diluent 45mL, decolorizing solution 1mL, staining solution A 0.5mL, staining solution B 1mL, PD-L1 (human) primary antibody 100 ⁇ L, goat antibody 100 ⁇ L of human IgG/HRP, 100 ⁇ L of 0.1% Triton X-100, 100 ⁇ L of 0.3% H 2 O 2 , 0.5 mL of reagent A, 60 mL of 6 ⁇ PBS buffer.
  • the composition of the diluent is: 1 mmol/L EDTA+0.1% BSA+0.1% trehalose+0.2% tyrosine+PBS buffer 150 mmol/L, wherein the percentage is a volume ratio.
  • the decolorizing liquid is composed of 95% alcohol and 100% xylene in a volume ratio of 1:1.
  • the staining solution A is a DAB staining solution
  • the staining solution B is a hematoxylin staining solution.
  • the reagent A is xylene.
  • the method for detecting PD-L1 gene mutations in peripheral blood circulating tumor cells of patients with gastric cancer for non-diagnostic purposes of the kit described above includes the following steps:
  • the specific method for detecting the expression of PD-L1 of CTC is as follows:
  • the membrane filtration device for separating tumor cells used in the present invention includes a filter, a blood sample container, a waste liquid cylinder, and an iron stand.
  • the iron stand is provided with a base, a stand and a bracket.
  • the blood sample container is set on the upper part of the iron stand through the bracket.
  • a filter which is connected to the waste liquid tank through the infusion set, and the waste liquid tank is arranged on the base.
  • the filter includes a filter upper port, a filter membrane, a filter membrane platform and a filter lower port.
  • the filter membrane is placed on the filter membrane platform; the upper port of the filter is connected to the blood sample container, and the lower port of the filter is connected to the waste liquid tank through the infusion device.
  • the filter membrane is made of a hydrophobic material, and the filter holes with a diameter of 8 micrometers are evenly spread on it.
  • the detection method provided by the present invention can detect PD-L1 expression in patients with advanced or recurrent gastric cancer without puncture biopsy to obtain tissue samples. This technology is minimally invasive and can be detected in real time.
  • the method provided by the present invention can avoid false positive results caused by edge effects that may occur during the staining process, has good stability, reduces cell loss, and improves detection accuracy.
  • Figure 1 is a schematic diagram of the structure of the membrane filtration device of the present invention.
  • FIG. 2 is a schematic cross-sectional view of the structure of the filter of the membrane filtration device of the present invention
  • FIG. 3 is a schematic diagram of the structure of the filter membrane of the membrane filtration device of the present invention.
  • Figure 4 is an image of circulating tumor cells obtained from the peripheral blood of a patient with gastric cancer
  • Figure 5 is a stained image of circulating tumor cells in the peripheral blood of a patient with advanced gastric cancer.
  • Component content 6 ⁇ PBS buffer 60mL Diluent 45mL Decolorizing liquid 1mL Staining solution A 0.5mL Staining Solution B 1mL PD-L1 (human) primary antibody (commercially available) 100 ⁇ L Goat anti-human IgG/HRP (commercially available) 100 ⁇ L 0.1% Triton X-100 100 ⁇ L 0.3% H 2 O 2 100 ⁇ L Reagent A 0.5mL
  • the membrane filtration device is composed of a filter 3, a filter membrane 7, a blood sample container 2, a waste liquid tank 5, and an iron stand 1;
  • the diameter of tumor cells is generally greater than 15 microns, and the diameter of blood cells (including red blood cells and white blood cells) is generally less than 8 microns. Therefore, after the peripheral blood containing CTC is filtered, the blood cells can be filtered because the diameter is smaller than the filter hole 10, and the CTC is larger than the diameter. The filter hole 10 is trapped on the filter membrane 7.
  • Figure 4 is an image of circulating tumor cells isolated from the peripheral blood of a gastric cancer patient.
  • the nucleus is large and the nucleus is irregular in shape; it has a high nucleus to cytoplasmic ratio.
  • nuclear atypia nuclear-to-plasma ratio greater than 0.8
  • cell diameter (long end) greater than 15um
  • hyperchromatic nuclei due to the increased chromatin of cancer cells, the particles become thicker and the nuclei are hyperchromatic).
  • Figure 5 is a stained image of circulating tumor cells in the peripheral blood of a patient with gastric cancer.
  • the detected circulating tumor cells were confirmed by immunohistochemistry for the expression of PD-L1 and compared with the results of PD-L1 in gross specimens of gastric cancer to observe the differences. It is mainly for patients with negative expression of PD-L1 in gross specimens and positive expression of circulating tumor cells.
  • Targeted therapy of gastric cancer provides new ideas for targeted therapy of gastric cancer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Analytical Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Hospice & Palliative Care (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne un kit et une méthode de détection permettant de détecter des mutations du gène PD-L1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique. Un dispositif de filtre membranaire est utilisé pour séparer et obtenir des CTC dans le sang périphérique d'un patient atteint d'un cancer gastrique avancé ou récurrent auprès duquel un échantillon tissulaire ne peut être obtenu, et une technologie d'immunohistochimie est en outre appliquée pour détecter l'expression PD-L1 des CTC. La méthode de détection selon la présente invention peut détecter l'expression de PD-L1 de patients atteints d'un cancer gastrique avancé ou récurrent sans biopsie par aspiration pour obtenir des échantillons tissulaires. La technologie est minimalement invasive et peut être utilisée pour une détection en temps réel. La méthode selon la présente invention peut éviter d'empêcher des résultats positifs provoqués par un effet de bord qui peut être généré au cours d'un processus de coloration, présente une bonne stabilité, réduit la perte de cellules et améliore la précision de détection.
PCT/CN2021/087719 2020-04-20 2021-04-16 Kit et méthode de détection permettant de détecter des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique WO2021213261A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010311970.9 2020-04-20
CN202010311970.9A CN111562376A (zh) 2020-04-20 2020-04-20 一种检测胃癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法

Publications (1)

Publication Number Publication Date
WO2021213261A1 true WO2021213261A1 (fr) 2021-10-28

Family

ID=72071773

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/087719 WO2021213261A1 (fr) 2020-04-20 2021-04-16 Kit et méthode de détection permettant de détecter des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique

Country Status (2)

Country Link
CN (1) CN111562376A (fr)
WO (1) WO2021213261A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111562376A (zh) * 2020-04-20 2020-08-21 山东第一医科大学(山东省医学科学院) 一种检测胃癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105588943A (zh) * 2016-01-28 2016-05-18 山东省肿瘤防治研究院 一种胃癌患者外周血循环肿瘤细胞Her-2基因的检测方法
CN106198984A (zh) * 2016-08-22 2016-12-07 上海立闻生物科技有限公司 非小细胞肺癌患者外周血循环肿瘤细胞pdl1基因的检测方法
WO2019089740A1 (fr) * 2017-11-03 2019-05-09 Dana-Farber Cancer Institute, Inc. Biomarqueurs de réponse clinique et de bienfait d'une thérapie par inhibiteur de point de contrôle immunitaire
CN110632292A (zh) * 2019-06-12 2019-12-31 江苏莱尔生物医药科技有限公司 一种检测pd-l1和cd8抗原的免疫荧光试剂盒及应用方法
CN111521798A (zh) * 2020-04-21 2020-08-11 山东第一医科大学(山东省医学科学院) 一种检测肾癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法
CN111562376A (zh) * 2020-04-20 2020-08-21 山东第一医科大学(山东省医学科学院) 一种检测胃癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法
CN111638341A (zh) * 2020-07-01 2020-09-08 山东凯歌智能机器有限公司 一种检测小细胞肺癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105588943A (zh) * 2016-01-28 2016-05-18 山东省肿瘤防治研究院 一种胃癌患者外周血循环肿瘤细胞Her-2基因的检测方法
CN106198984A (zh) * 2016-08-22 2016-12-07 上海立闻生物科技有限公司 非小细胞肺癌患者外周血循环肿瘤细胞pdl1基因的检测方法
WO2019089740A1 (fr) * 2017-11-03 2019-05-09 Dana-Farber Cancer Institute, Inc. Biomarqueurs de réponse clinique et de bienfait d'une thérapie par inhibiteur de point de contrôle immunitaire
CN110632292A (zh) * 2019-06-12 2019-12-31 江苏莱尔生物医药科技有限公司 一种检测pd-l1和cd8抗原的免疫荧光试剂盒及应用方法
CN111562376A (zh) * 2020-04-20 2020-08-21 山东第一医科大学(山东省医学科学院) 一种检测胃癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法
CN111521798A (zh) * 2020-04-21 2020-08-11 山东第一医科大学(山东省医学科学院) 一种检测肾癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法
CN111638341A (zh) * 2020-07-01 2020-09-08 山东凯歌智能机器有限公司 一种检测小细胞肺癌患者外周血循环肿瘤细胞pd-l1基因突变的试剂盒及检测方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIU MENGYUAN, WANG RUOYU, SUN XUREN, LIU YUTING, WANG ZHI, YAN JIN, KONG XIANGYU, LIANG SHANSHAN, LIU QIUGE, ZHAO TONG, JI XUENING: "Prognostic significance of PD-L1 expression on cell -surface vimentin- positive circulating tumor cells in gastric cancer patients", MOLECULAR ONCOLOGY, vol. 14, no. 4, 28 February 2020 (2020-02-28), pages 865 - 881, XP009531581, ISSN: 1878-0261, DOI: 10.1002/1878-0261.12643 *

Also Published As

Publication number Publication date
CN111562376A (zh) 2020-08-21

Similar Documents

Publication Publication Date Title
WO2021213316A1 (fr) Kit de détection d'une mutation du gène pd-l1 de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du rein, et procédé de détection
WO2021213323A1 (fr) Procédé non diagnostique de détection d'une mutation du gène pd-l1 chez un patient atteint d'un cancer colorectal au moyen de cellules tumorales circulantes dans le sang périphérique
WO2022001824A1 (fr) Kit et procédé de détection de mutations du gène pd-l1 dans des cellules tumorales circulantes dans le sang périphérique d'un patient atteint d'un cancer du poumon à petites cellules
WO2021213262A1 (fr) Kit de test d'immunofluorescence pour mesurer l'expression de pd-l1 dans des cellules tumorales circulantes dans le sang périphérique d'un patient atteint d'un cancer de l'estomac et procédé de mesure
WO2021213322A1 (fr) Kit d'immunofluorescence pour détecter l'expression pd-l1 de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du rein et procédé de détection
WO2021213292A1 (fr) Kit de test d'immunofluorescence permettant de mesurer l'expression de pd-l1 dans des cellules tumorales circulantes dans le sang périphérique chez un patient atteint d'un cancer de la prostate, et méthode de mesure
WO2021213295A1 (fr) Kit d'immunofluorescence pour détecter une mutation du gène nse de cellules tumorales circulantes du sang périphérique chez un patient atteint d'un cancer du poumon à petites cellules et procédé de détection
WO2021213306A1 (fr) Kit de test pour mesurer des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique chez un patient atteint d'un cancer du poumon non à petites cellules, et procédé de mesure
WO2021213304A1 (fr) Kit de détection de mutation de gène nse de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du poumon à petites cellules et procédé de détection
WO2021213297A1 (fr) Kit de test d'immunofluorescence pour mesurer des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique chez un patient atteint d'un cancer du poumon non à petites cellules, et procédé associé
WO2021213290A1 (fr) Kit pour tester l'expression de ca199 dans des cellules tumorales circulantes dans le sang périphérique de patients atteints d'un cancer du pancréas et procédé de test
WO2021213302A1 (fr) Kit de test d'immunofluorescence pour mesurer des mutations du gène cea dans des cellules tumorales circulantes du sang périphérique chez un patient atteint d'un cancer du poumon non à petites cellules, et procédé de mesure
WO2021213310A1 (fr) Kit d'immunofluorescence pour la détection de l'expression du gѐne pd-l1 chez un patient atteint d'un carcinome épidermoïde œsophagien au moyen de cellules tumorales circulantes du sang périphérique
WO2022001825A1 (fr) Kit pour détecter l'expression de e-cadhérine de cellules tumorales circulantes dans le sang périphérique d'un patient atteint d'un cancer du pancréas et méthode de détection
WO2021213315A1 (fr) Kit de détection de l'expression de mutation du gène braf v600e d'un patient atteint d'un cancer colorectal au moyen de cellules tumorales circulantes du sang périphérique
WO2021233037A1 (fr) Kit de détection de mutation de gène fgfr de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du canal biliaire et méthode de détection associée
WO2021213261A1 (fr) Kit et méthode de détection permettant de détecter des mutations du gène pd-l1 dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer gastrique
WO2021213299A1 (fr) Kit de détection de mutation du gène pd-l1 de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer de la prostate, et procédé de détection
WO2021213318A1 (fr) Procédé non-diagnostique pour mesurer des mutations du gène braf v600e chez un patient atteint d'un cancer colorectal au moyen de cellules tumorales circulantes dans le sang périphérique
WO2022001823A1 (fr) Trousse et méthode de détection de mutations du gène de l'e-cadhérine dans des cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du poumon non à petites cellules
WO2021213311A1 (fr) Kit d'immunofluorescence permettant la détection de l'expression génique pd-l1 d'un patient atteint d'un cancer colorectal au moyen de cellules tumorales circulantes du sang périphérique
WO2022001826A1 (fr) Kit d'immunofluorescence pour la détection de l'expression de e-cadhérine de cellules tumorales circulantes dans le sang périphérique d'un patient atteint d'un cancer du pancréas
WO2021213298A1 (fr) Kit d'immunofluorescence permettant de détecter l'expression ca199 de cellules tumorales circulantes du sang périphérique d'un patient atteint d'un cancer du pancréas et méthode de détection
CN111534586B (zh) 一种检测非小细胞肺癌患者外周血循环肿瘤细胞cea基因突变的试剂盒及检测方法
CN111638344A (zh) 检测小细胞肺癌患者外周血循环肿瘤细胞E-Cadherin基因突变的试剂盒及方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21793103

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21793103

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC

122 Ep: pct application non-entry in european phase

Ref document number: 21793103

Country of ref document: EP

Kind code of ref document: A1