WO2013025589A1 - Procédés et compositions pour le diagnostic et le pronostic d'un cancer gastrique - Google Patents

Procédés et compositions pour le diagnostic et le pronostic d'un cancer gastrique Download PDF

Info

Publication number
WO2013025589A1
WO2013025589A1 PCT/US2012/050540 US2012050540W WO2013025589A1 WO 2013025589 A1 WO2013025589 A1 WO 2013025589A1 US 2012050540 W US2012050540 W US 2012050540W WO 2013025589 A1 WO2013025589 A1 WO 2013025589A1
Authority
WO
WIPO (PCT)
Prior art keywords
gastric cancer
population
assay
patient
threshold level
Prior art date
Application number
PCT/US2012/050540
Other languages
English (en)
Inventor
Brian Thomas MISINER
Kelline Marie Rodems
William D. Arnold
Brian Noland
Original Assignee
Alere San Diego, Inc.
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 Alere San Diego, Inc. filed Critical Alere San Diego, Inc.
Publication of WO2013025589A1 publication Critical patent/WO2013025589A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57446—Specifically defined cancers of stomach or intestine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/50—Determining the risk of developing a disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/54—Determining the risk of relapse

Definitions

  • Preferred assays are "configured to detect" a particular marker. That an assay is “configured to detect” a marker means that an assay can generate a detectable signal indicative of the presence or amount of a physiologically relevant concentration of a particular marker of interest. Such an assay may, but need not, specifically detect a particular marker ⁇ i.e., detect a marker but not some or all related markers). Because an antibody epitope is on the order of 8 amino acids, an immunoassay will detect other polypeptides ⁇ e.g., related markers) so long as the other polypeptides contain the epitope(s) necessary to bind to the antibody used in the assay.
  • test sample refers to a sample of bodily fluid obtained for the purpose of diagnosis, prognosis, or evaluation of a subject of interest, such as a patient. In certain embodiments, such a sample may be obtained for the purpose of determining the outcome of an ongoing condition or the effect of a treatment regimen on a condition.
  • Preferred test samples include blood, serum, plasma, cerebrospinal fluid, urine, saliva, sputum, gastric juices, and pleural effusions.
  • test samples would be more readily analyzed following a fractionation or purification procedure, for example, separation of whole blood into serum or plasma components.
  • diagnosis refers to an increased probability that a certain disease is present in the subject.
  • the sample's marker level can be compared to a marker level known to be associated with a good outcome (e.g. , the absence of disease, etc.).
  • a profile of marker levels are correlated to a global probability or a particular outcome using ROC curves.
  • the methods described herein comprise the comparison of an assay result to a corresponding baseline result.
  • baseline result refers to an assay value that is used as a comparison value (that is, to which a test result is compared). In practical terms, this means that a marker is measured in a sample from a subject, and the result is compared to the baseline result. A value above the baseline indicates a first likelihood of a diagnosis or prognosis, and a value below the baseline indicates a second likelihood of a diagnosis or prognosis.
  • a baseline marker level is established for a subject, and a subsequent assay result for the same marker is determined. That subsequent result is compared to the baseline result, and a value above the baseline indicates worsening cardiac function, relative to a value below the baseline. Similarly, a value below the baseline indicates improved cardiac function, relative to a value above the baseline.
  • a baseline marker level is established for a subject, and a subsequent assay result for the same marker is determined. That subsequent result is compared to the baseline result, and a value above the baseline indicates an increased mortality risk, relative to a value below the baseline. Similarly, a value below the baseline indicates a decreased mortality risk, relative to a value above the baseline.
  • the measurement of the level of a single marker may be augmented by additional markers.
  • Various clinical variables may also be utilized as variables in the methods described herein. Examples of such variables include stage of the gastric cancer identified histologically, smoking status, etc. This list is not meant to be limiting.
  • marker above its corresponding baseline value may signal a gastric cancer diagnosis or an increased risk of an adverse outcome (in n-of-m terms, this is a "l-of-2" result). If both are above the corresponding baselines (a "2-of-2" result), an even greater confidence in the subject's status may be indicated.
  • markers and/or marker panels are preferably selected to exhibit an odds ratio of at least about 2 or more or about 0.5 or less, more preferably at least about 3 or more or about 0.33 or less, still more preferably at least about 4 or more or about 0.25 or less, even more preferably at least about 5 or more or about 0.2 or less, and most preferably at least about 10 or more or about 0.1 or less.
  • the term "about” in this context refers to +/- 5% of a given measurement.
  • immunoassay analyzers that are capable of performing the immunoassays taught herein.
  • the markers are analyzed using an immunoassay, and most preferably sandwich immunoassay, although other methods are well known to those skilled in the art (for example, the measurement of marker RNA levels).
  • the presence or amount of a marker is generally determined using antibodies specific for each marker and detecting specific binding.
  • Any suitable immunoassay may be utilized, for example, enzyme-linked immunoassays (ELISA), radioimmunoassays (RIAs), competitive binding assays, and the like. Specific immunological binding of the antibody to the marker can be detected directly or indirectly.
  • Biological assays such as immunoassays require methods for detection, and one of the most common methods for quantitation of results is to conjugate an enzyme, fluorophore or other molecule to form an antibody-label conjugate.
  • Detectable labels may include molecules that are themselves detectable (e.g., fluorescent moieties, electrochemical labels, metal chelates, etc.) as well as molecules that may be indirectly detected by production of a detectable reaction product (e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.) or by a specific binding molecule which itself may be detectable (e.g., biotin, digoxigenin, maltose, oligohistidine, 2,4- dintrobenzene, phenylarsenate, ssDNA, dsDNA, etc.).
  • a detectable reaction product e.g., enzymes such as horseradish peroxidase, alkaline phosphatase, etc.
  • detectable labels are fluorescent latex particles such as those described in U.S. Patents 5,763,189, 6,238,931, and 6,251,687; and International Publication WO95/08772, each of which is hereby incorporated by reference in its entirety. Exemplary conjugation to such particles is described hereinafter.
  • Direct labels include fluorescent or luminescent tags, metals, dyes, radionuclides, and the like, attached to the antibody.
  • Indirect labels include various enzymes well known in the art, such as alkaline phosphatase, horseradish peroxidase and the like.
  • solid phase refers to a wide variety of materials including solids, semi-solids, gels, films, membranes, meshes, felts, composites, particles, papers and the like typically used by those of skill in the art to sequester molecules.
  • the solid phase can be non-porous or porous. Suitable solid phases include those developed and/or used as solid phases in solid phase binding assays. See, e.g., chapter 9 of Immunoassay, E. P. Dianiandis and T. K. Christopoulos eds., Academic Press: New York, 1996, hereby incorporated by reference.
  • suitable solid phases include membrane filters, cellulose-based papers, beads (including polymeric, latex and paramagnetic particles), glass, silicon wafers, microparticles, nanoparticles, TentaGels, AgroGels, PEGA gels, SPOCC gels, and multiple-well plates.
  • membrane filters e.g., Leon et al, Bioorg. Med. Chem. Lett. 8: 2997, 1998; Kessler et al, Agnew. Chem. Int. Ed. 40: 165, 2001 ; Smith et al, J. Comb. Med. 1 : 326, 1999; Orain et al, Tetrahedron Lett. 42: 515, 2001 ; Papanikos et al, J. Am.
  • the antibodies could be immobilized onto a variety of solid supports, such as magnetic or chromatographic matrix particles, the surface of an assay place (such as microtiter wells), pieces of a solid substrate material or membrane (such as plastic, nylon, paper), and the like.
  • An assay strip could be prepared by coating the antibody or a plurality of antibodies in an array on solid support. This strip could then be dipped into the test sample and then processed quickly through washes and detection steps to generate a measurable signal, such as a colored spot.
  • a plurality of separately addressable locations each corresponding to a different marker and comprising antibodies that bind the appropriate marker, can be provided on a single solid support.
  • discrete refers to areas of a surface that are non-contiguous. That is, two areas are discrete from one another if a border that is not part of either area completely surrounds each of the two areas.
  • independently addressable refers to discrete areas of a surface from which a specific signal may be obtained.
  • suitable apparatuses include clinical laboratory analyzers such as the ElecSys (Roche), the AxSym (Abbott), the Access (Beckman), the ADVIA® CENTAUR® (Bayer) immunoassay systems, the NICHOLS ADVANTAGE® (Nichols Institute) immunoassay system, etc.
  • Preferred apparatuses perform simultaneous assays of a plurality of markers using a single test device.
  • Particularly useful physical formats comprise surfaces having a plurality of discrete, adressable locations for the detection of a plurality of different analytes.
  • Such formats include protein microarrays, or "protein chips" (see, e.g., Ng and Hag, J. Cell Mol.
  • each discrete surface location may comprise antibodies to immobilize one or more analyte(s) (e.g., a marker) for detection at each location.
  • Surfaces may alternatively comprise one or more discrete particles (e.g., microparticles or nanoparticles) immobilized at discrete locations of a surface, where the microparticles comprise antibodies to immobilize one analyte (e.g., a marker) for detection.
  • Preferred assay devices of the present invention will comprise, for one or more assays, a first antibody conjugated to a solid phase and a second antibody conjugated to a signal development element. Such assay devices are configured to perform a sandwich immunoassay for one or more analytes. These assay devices will preferably further comprise a sample application zone, and a flow path from the sample application zone to a second device region comprising the first antibody conjugated to a solid phase.
  • Flow of a sample in an assay device along the flow path may be driven passively (e.g., by capillary, hydrostatic, or other forces that do not require further manipulation of the device once sample is applied), actively (e.g., by application of force generated via mechanical pumps, electroosmotic pumps, centrifugal force, increased air pressure, etc.), or by a combination of active and passive driving forces.
  • sample applied to the sample application zone will contact both a first antibody conjugated to a solid phase and a second antibody conjugated to a signal development element along the flow path (sandwich assay format). Additional elements, such as filters to separate plasma or serum from blood, mixing chambers, etc., may be included as required by the artisan.
  • the present invention provides a kit for the analysis of markers.
  • a kit for the analysis of markers preferably comprises devises and reagents for the analysis of at least one test sample and instructions for performing the assay(s) of intrest.
  • kits may contain one or more means for using information obtained from immunoassays or other specific binding assays performed for a marker panel to rule in or out certain diagnoses or prognoses.
  • Other measurement strategies applicable to the methods described herein include chromatography (e.g., HPLC), mass spectrometry, receptor-based assays, and combinations of the foregoing.
  • a dAb fragment (Ward et al., (1989) Nature 341 :544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR).
  • Single chain antibodies are also included by reference in the term "antibody.” While the present invention is described in detail in terms of immunologic detection of an analyte, other marker binding partners such as aptamers, receptors, binding proteins, etc., may be used in a similar fashion to antibodies in providing an assay. [0058] Preferably, an antibody or other binding partner used in an assay is selected that specifically binds a marker of interest. The term “specifically binds" is not intended to indicate that an antibody/binding partner binds exclusively to its intended target.
  • r/c is plotted on the Y-axis versus r on the X-axis thus producing a Scatchard plot.
  • the affinity is the negative slope of the line.
  • k c ff can be determined by competing bound labeled ligand with unlabeled excess ligand (see, e.g., U.S. Pat No. 6,316,409).
  • the selected polypeptides may then be injected, for example, into mice or rabbits, to generate polyclonal or monoclonal antibodies.
  • injected for example, into mice or rabbits, to generate polyclonal or monoclonal antibodies.
  • One skilled in the art will recognize that many procedures are available for the production of antibodies, for example, as described in Antibodies, A Laboratory Manual, Ed Harlow and David Lane, Cold Spring Harbor Laboratory (1988), Cold Spring Harbor, N.Y.
  • binding fragments or Fab fragments which mimic antibodies can also be prepared from genetic information by various procedures (Antibody Engineering: A Practical Approach (Borrebaeck, C, ed.), 1995, Oxford University Press, Oxford; J. Immunol. 149, 3914-3920 (1992)).
  • the antibodies so identified may then be further analyzed for affinity and specificity in the assay design selected.
  • the purified target protein acts as a standard with which to judge the sensitivity and specificity of the immunoassay using the antibodies that have been selected. Because the binding affinity of various antibodies may differ; certain antibody pairs (e.g., in sandwich assays) may interfere with one another sterically, etc., assay performance of an antibody may be a more important measure than absolute affinity and specificity of an antibody.
  • Nucleic acid aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection or equivalently, SELEX (systematic evolution of ligands by exponential enrichment) to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms.
  • Peptide aptamers are proteins that are designed to interfere with other protein interactions inside cells. They consist of a variable peptide loop attached at both ends to a protein scaffold. This double structural constraint greatly increases the binding affinity of the peptide aptamer to levels comparable to an antibody's (nanomolar range). Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of the commonly used biomolecule, antibodies.
  • a source plate was made by thawing the sample plate at 37 ° C, and then adding replicates of the 8-point calibration curve. [0070] The assays were performed at room temperature. The bead-based primary antibody solution was added to a 384-well assay plate (lOul/well) and then samples were added from the source plate (lOul/well), mixed, and incubated one hour. Note, competitive assays were run in different assay plates than the sandwich assays, and the biotinylated antigen was added to the samples before transfer to the assay plate. Each 384-well plate was split into four 96-well plates for subsequent processing.
  • Calibrators were assayed in the same manner as the sample population specimens, and the resulting data used to construct a "dose-response" curve (assay signal as a function of analyte concentration), which may be used to determine analyte concentrations from assay signals obtained from subject specimens.
  • dose-response assay signal as a function of analyte concentration
  • Another monoclonal antibody directed against the same analyte was conjugated to alkaline phosphatase, for example using succinimidyl 4-[N- maleimidomethyl]-cyclohexane-l-carboxylate (SMCC) and N- succinimidyl 3-[2- pyridyldithiojpropionate (SPDP) (Pierce, Rockford, IL).
  • SMCC succinimidyl 4-[N- maleimidomethyl]-cyclohexane-l-carboxylate
  • SPDP 2- pyridyldithiojpropionate
  • ROC AUC or Odds ratio results were chosen to be included as covariates for the purpose of adjusting multi-marker Odds Ratios.
  • the selected risk factors were Age, Tobacco Use, History of Atrophic Gastritis and H.pylori Infection.

Landscapes

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

Abstract

La présente invention concerne des procédés pour diagnostiquer un cancer gastrique ; des procédés pour attribuer un risque de récurrence d'un cancer gastrique ; des procédés pour attribuer un risque de mortalité dû à un cancer gastrique, des procédés de surveillance d'un cancer gastrique ; des procédés de stadification d'un cancer gastrique ; et différents dispositifs et trousses conçus pour réaliser de tels procédés. Ces procédés comprennent la mesure du facteur en trèfle (1) et, de manière facultative, d'un homologue de protéine de gradient antérieur (2) sur un échantillon de liquide organique obtenu à partir d'un sujet.
PCT/US2012/050540 2011-08-13 2012-08-13 Procédés et compositions pour le diagnostic et le pronostic d'un cancer gastrique WO2013025589A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161523290P 2011-08-13 2011-08-13
US61/523,290 2011-08-13

Publications (1)

Publication Number Publication Date
WO2013025589A1 true WO2013025589A1 (fr) 2013-02-21

Family

ID=47715409

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/050540 WO2013025589A1 (fr) 2011-08-13 2012-08-13 Procédés et compositions pour le diagnostic et le pronostic d'un cancer gastrique

Country Status (1)

Country Link
WO (1) WO2013025589A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113466465A (zh) * 2021-01-20 2021-10-01 浙江大学滨海产业技术研究院 一种基于蛋白质组学的唾液检测方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080050832A1 (en) * 2004-12-23 2008-02-28 Buechler Kenneth F Methods and compositions for diagnosis and/or prognosis in systemic inflammatory response syndromes
US20080057514A1 (en) * 2006-09-06 2008-03-06 Vanderbilt University Methods of screening for gastrointestinal cancer
US20080182259A1 (en) * 2007-01-15 2008-07-31 Sysmex Corporation Method for judging lymph node metastasis of stomach cancer and kit used therefor

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080050832A1 (en) * 2004-12-23 2008-02-28 Buechler Kenneth F Methods and compositions for diagnosis and/or prognosis in systemic inflammatory response syndromes
US20080057514A1 (en) * 2006-09-06 2008-03-06 Vanderbilt University Methods of screening for gastrointestinal cancer
US20080182259A1 (en) * 2007-01-15 2008-07-31 Sysmex Corporation Method for judging lymph node metastasis of stomach cancer and kit used therefor

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113466465A (zh) * 2021-01-20 2021-10-01 浙江大学滨海产业技术研究院 一种基于蛋白质组学的唾液检测方法

Similar Documents

Publication Publication Date Title
US11977077B2 (en) Biomarkers for pancreatic cancer
US8795975B2 (en) Methods and compositions for diagnosis and risk prediction in heart failure
US20140315734A1 (en) Methods and compositions for assigning likelihood of acute kidney injury progression
Song et al. Identification of serum biomarker panels for the early detection of pancreatic cancer
US20100272635A1 (en) Methods and compositions for diagnosis and/or prognosis in ovarian cancer and lung cancer
EP2095106A2 (fr) Procedes et compositions de diagnostic et de pronostic de la stenose d'artere renale
US10794917B2 (en) Methods and compositions for diagnosis and prognosis of appendicitis and differentiation of causes of abdominal pain
WO2009006347A2 (fr) Procédés et compositions pour le diagnostic et/ou le pronostic dans des syndromes de réponse inflammatoire systémique
US20150309052A1 (en) Acute kidney injury
WO2015164616A1 (fr) Biomarqueurs de détection de la tuberculose
AU2017260806B9 (en) Markers of endometrial cancer
EP3655778B1 (fr) Agrin en tant que marqueur du cancer endometrial
US20150285804A1 (en) Diagnostic method for colorectal cancer
WO2013096740A1 (fr) Procédés et compositions destinés à attribuer une probabilité de progression de maladie rénale chronique
WO2013025589A1 (fr) Procédés et compositions pour le diagnostic et le pronostic d'un cancer gastrique
EP3311164B1 (fr) Méthodes et compositions pour le diagnostic et le pronostic de l'appendicite et la différenciation des causes de la douleur abdominale
WO2022128881A1 (fr) Biomarqueurs prédictifs du risque de cancer de la vessie chez des patients atteints de diabète
BR122023026792A2 (pt) Método e uso da combinação dos marcadores perm e clic1 como marcadores in vitro para diagnosticar ou prognosticar carcinoma endometrial, bem como kit para detectar nível de expressão proteica

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: 12824577

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: 12824577

Country of ref document: EP

Kind code of ref document: A1