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1. 发明申请

WO2012097276A2 BCL-2-LIKE PROTEIN 11 SRM/MRM ASSAY 审中-公开
标题翻译： BCL-2样蛋白11 SRM / MRM测定
公开(公告)号：WO2012097276A2
公开(公告)日：2012-07-19
申请号：PCT/US2012/021283
申请日：2012-01-13
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
IPC分类号： C12Q1/37
CPC分类号： G01N33/6893 , C07K14/4747 , C07K16/2863 , C07K16/32 , C07K2317/76 , C12Q1/485 , C12Q1/6886 , C12Q2600/158 , G01N33/5088 , G01N33/574 , G01N33/6848 , G01N2333/4703 , G01N2800/44 , G01N2800/52 , G01N2800/56
摘要： Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin- fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol, and the BIM protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：提供了来自Bcl-2样蛋白11（BIM）的那些肽的特异性肽和衍生的电离特征，其特别有利于通过选择反应的方法在福尔马林中固定的生物样品中直接定量BIM蛋白监测（SRM）质谱，或什么也可以称为多反应监测（MRM）。在生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从生物样品制备蛋白质样品，并且通过SRM / MRM质谱法通过在蛋白质样品中定量至少一种或多种的蛋白质样品，在Liquid TissueTM样品中定量BIM蛋白质描述的肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 BIM肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

2. 发明申请

WO2011087865A1 EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： EPIDERM生长因子受体（EGFR）蛋白SRM / MRM测定
公开(公告)号：WO2011087865A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061916
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N33/50
CPC分类号： G01N33/6863 , A61K31/517 , A61K31/5377 , C07K14/71 , C07K16/2863 , C07K2317/24 , G01N33/57407 , G01N33/6842 , G01N33/6848 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2560/00
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Epidermal Growth Factor Receptor (EGFR) protein that are particularly advantageous for quantifying the EGFR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the EGFR protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an EGFR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自表皮生长因子受体（EGFR）蛋白质的特定肽和衍生的离子化特征，其特别有利于通过所选择的方法在福尔马林中固定的生物样品中直接定量EGFR蛋白质反应监测（SRM）质谱法，还可以称作多反应监测（MRM）质谱。这些生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品中制备蛋白质样品，并且通过SRM / MRM质谱法的方法将蛋白质定量在液体组织样品中，通过在蛋白质样品中定量至少一种或多种肽描述。如果它们以修饰或未修饰的形式存在，则可定量这些肽。 EGFR肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化。

3. 发明申请

WO2012092531A1 HER3 PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： HER3蛋白SRM / MRM测定
公开(公告)号：WO2012092531A1
公开(公告)日：2012-07-05
申请号：PCT/US2011/067998
申请日：2011-12-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： C07K16/18
CPC分类号： G01N33/6848 , G01N33/574 , G01N33/6893 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2333/912 , G01N2333/9121
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3. that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
摘要翻译：目前的公开内容提供了来自受体酪氨酸 - 蛋白激酶erbB-3或Her3的肽的特定肽和衍生的电离特征。这特别有利于通过选择反应监测（SRM）质谱法或还可以称作多重反应监测（MRM）质谱法的方法，在已经在福尔马林中固定的生物样品中直接定量Her3蛋白。这样的生物样品是化学保存和固定的，其中所述生物样品选自用含甲醛的试剂固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块和细胞）处理的组织和细胞从那些块和已经被福尔马林固定和石蜡包埋的组织培养细胞。

4. 发明申请

WO2011087868A1 INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR (IGF-1R) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译：胰岛素样生长因子1受体（IGF-1R）蛋白SRM / MRM测定
公开(公告)号：WO2011087868A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061924
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N33/50
CPC分类号： G01N33/6851 , G01N33/6848 , G01N33/74 , G01N2333/71
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Insulin-Like Growth Factor 1 Receptor (IGF- I R) protein that are particularly advantageous for quantifying the IGF-IR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin- fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the IGF- I R protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IGF-I R peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供来自胰岛素样生长因子1受体（IGF-1R）蛋白的特定肽和衍生的电离特征，其特别有利于直接在固定的生物样品中对IGF-1R蛋白进行定量在福尔马林中，通过选择反应监测（SRM）质谱法或还可以称为多反应监测（MRM）质谱法。这样的生物样品是化学保存和固定的，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在液体组织样品中定量IGF-1R蛋白，通过在蛋白质样品中定量至少一种或多种描述的肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 IGF-I R肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

5. 发明申请

WO2011087869A1 SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE (SPARC) PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译：分泌蛋白酸和CYCTEINE（SPARC）蛋白SRM / MRM测定
公开(公告)号：WO2011087869A1
公开(公告)日：2011-07-21
申请号：PCT/US2010/061925
申请日：2010-12-22
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： G01N31/00 , A61K38/00
CPC分类号： G01N33/68 , A61K38/08 , A61K38/10 , C07K7/06 , C07K7/08 , C07K14/47 , C07K16/18 , G01N33/6851 , G01N33/6887 , G01N2333/4727 , G01N2333/96433
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein that are particularly advantageous for quantifying the SPARC protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fϊxed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue TM reagents and protocol and the SPARC protein is quantitated in the Liquid Tissue TM sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an SPARC peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自分泌蛋白酸性和富含半胱氨酸（SPARC）蛋白质的肽的特定肽和衍生的电离特征，其特别有利于直接在通过由福尔马林固定在福尔马林中的生物样品中量化SPARC蛋白选择反应监测（SRM）质谱法的方法，或也称为多反应监测（MRM）质谱的方法。这样的生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织）处理的组织和细胞块和来自这些块的细胞，以及已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid TissueTM试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在SPT蛋白质中定量SPARC蛋白质，通过在蛋白质样品中定量至少一种或多种肽描述。如果它们以修饰或未修饰的形式存在，则可定量这些肽。 SPARC肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化。

6. 发明申请

WO2012016182A1 C-SRC SELECTED REACTION MONITORING ASSAY 审中-公开
标题翻译： C-SRC选择的反应监测测定
公开(公告)号：WO2012016182A1
公开(公告)日：2012-02-02
申请号：PCT/US2011/045960
申请日：2011-07-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B.
发明人： KRIZMAN, David, B.
IPC分类号： G01N33/483 , G01N30/72
CPC分类号： C12Q1/485 , G01N33/6848 , G01N2333/91205
摘要： Objective quantitation of the c-Src protein directly in cancer patient tissue can aid in determining die aggressiveness of an individual patient's tumor as well as help make more informed decisions about choice of therapy. However, fee c-Src protein is currently analyzed directly in formalin fixed patient tissue only by immunohistoehemistry methodology which is at best subjectively semi-quantitative. This invention describes an objective quantitative assay for the c-Sre protein using mass spectrometry as the analytical methodology, Specific peptides, experimentally discovered characteristics about the peptides, and experimentally established assay conditions based on those peptide characteristics are provided for use in a mass speetronieiry-based Selected Reaction Monitoring (SRM) assay in order to measure relative- or absolute quantitative levels of c-Src directly in a protein preparation obtained from a formalin fixed cancer patient tissue sample.
摘要翻译： c-Src蛋白直接在癌症患者组织中的客观定量可以帮助确定个体患者肿瘤的侵袭性，并帮助对治疗选择作出更明智的决定。然而，费用c-Src蛋白质目前仅在福尔马林固定患者组织中通过免疫组织化学方法进行直接分析，该方法最多在主观上半定量。本发明描述了使用质谱法作为分析方法的c-Sre蛋白质的客观定量测定法，特异性肽，关于肽的实验发现的特征以及基于这些肽特征的实验建立的测定条件被提供用于大规模特异性 - 基于选择反应监测（SRM）测定，以便直接在从福尔马林固定的癌症患者组织样品获得的蛋白质制剂中测量c-Src的相对或绝对定量水平。

7. 发明申请

WO2006127860A2 MULTIPLEX METHOD FOR INCREASED PROTEOMIC COVERAGE FROM HISTOPATHOLOGICALLY PROCESSED BIOLOGICAL SAMPLES USING LIQUID TISSUE PREPARATIONS 审中-公开
标题翻译：使用液体组织制剂从组织病理学处理的生物样品中增加保护性覆盖物的多重方法
公开(公告)号：WO2006127860A2
公开(公告)日：2006-11-30
申请号：PCT/US2006/020166
申请日：2006-05-25
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , GUIEL, Thomas, G. , DARFLER, Marlene, M.
发明人： KRIZMAN, David, B. , GUIEL, Thomas, G. , DARFLER, Marlene, M.
IPC分类号： G01N33/574 , G01N33/53
CPC分类号： G01N33/6803 , G01N1/30 , G01N33/6848
摘要： The invention provides methods for multiplex analysis of biological samples of formalin-fixed tissue samples. The invention provides for a method to achieve a multiplexed, multi-staged plurality of Liquid Tissue preparations simultaneously from a single histopathologically processed biological sample, where the protocol for each Liquid Tissue preparation imparts a distinctive set of biochemical effects on biomolecules procured from histopathologically processed biological samples and which when each of the preparations is analyzed can render additive and complementary data about the same histopathologically processed biological sample.
摘要翻译：本发明提供了福尔马林固定组织样品的生物样品的多重分析方法。本发明提供了一种从单一组织病理学处理的生物样品同时获得多重多级液体组织制剂的方法，其中每种液体组织制剂的方案对从组织病理学处理的生物学样品中获得的生物分子赋予特殊的生物化学效应样品以及当分析每种制剂时可以提供关于相同组织病理学处理的生物样品的添加剂和补充数据。

8. 发明申请

WO2012092529A2 PROTEIN BIOMARKERS OF RECURRENT BREAST CANCER 审中-公开
标题翻译：乳腺癌的蛋白质生物标志物
公开(公告)号：WO2012092529A2
公开(公告)日：2012-07-05
申请号：PCT/US2011/067996
申请日：2011-12-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , DARFLER, Marlene, M. , CONRADS, Thomas, P. , HOOD, Brian, L. , BATEMAN, Nicholas, W.
发明人： KRIZMAN, David, B. , DARFLER, Marlene, M. , CONRADS, Thomas, P. , HOOD, Brian, L. , BATEMAN, Nicholas, W.
IPC分类号： C12Q1/37
CPC分类号： G01N33/57415 , C12Q1/6886 , C12Q2600/118 , C12Q2600/156 , G01N2800/52
摘要： This patent application discloses and describes proteins found to be differentially expressed between primary tumor breast cancer cells that did not give rise to recurrent breast cancer disease after initial diagnosis and primary breast cancer cells that did give rise to recurrent breast cancer disease after initial diagnosis. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from breast cancer patients to indicate the likelihood that a breast cancer patient's cancer will recur after initial diagnosis and treatment. Determination of differential expression of these proteins can also be useful for indicating additional therapies to combat the likelihood of recurrent breast cancer. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein the differentially expressed proteins that arc used as diagnostic and prognostic indicators can also be used as targets for therapeutic intervention of breast cancer. Also disclosed and described herein are isotope labeled versions of peptides from the proteins.
摘要翻译：该专利申请公开并描述了在初步诊断后不会引起复发性乳腺癌疾病的原发性乳腺癌细胞和初次诊断后引起复发性乳腺癌疾病的原发性乳腺癌细胞之间发现差异表达的蛋白质。这些蛋白质可以在乳腺癌患者的各种生物样品的诊断和预后蛋白质测定中单独使用或以特定组合使用，以指示乳腺癌患者的癌症在初步诊断和治疗后将复发的可能性。确定这些蛋白质的差异表达也可用于指示额外的治疗方法来抵抗复发性乳腺癌的可能性。可以测定全长完整蛋白质，或者可以将这些蛋白质衍生的肽作为这些蛋白质的报告物进行测定。这些蛋白质也可以被鉴定为“伴侣诊断”蛋白质，其中用作诊断和预后指标的差异表达的蛋白质也可以用作乳腺癌的治疗干预的靶标。本文还公开和描述的是来自蛋白质的肽的同位素标记形式。

9. 发明申请

WO2011150245A2 UROKINASE-TYPE PLASMINOGEN ACTIVATOR PROTEIN/PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 PROTEIN-SELECTED REACTION MONITORING ASSAY 审中-公开
标题翻译： UROKINASE型类PLASMINOGEN激活蛋白/ PLASMINOGEN激活剂抑制剂类型1蛋白质选择的反应监测测定
公开(公告)号：WO2011150245A2
公开(公告)日：2011-12-01
申请号：PCT/US2011/038196
申请日：2011-05-26
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B.
发明人： KRIZMAN, David, B.
IPC分类号： C12Q1/37
CPC分类号： C12Q1/37 , G01N2333/8132 , G01N2333/972
摘要： Specific peptides are provided that are derived from subsequences of the urokinase-type plasminogen activator protein and the plasminogen activator inhibitor type-1 protein along with assays that can measure those peptides directly in complex protein lysate samples, including protein lysates prepared from histologicaly-processed formalin fixed tissue. The presence and amount of those peptides in samples from a subject can be associated with disease, including cancer, in a subject and provide information about the diagnostic stage/grade/status of the disease/cancer.
摘要翻译：提供了特异性肽，其衍生自尿激酶型纤溶酶原激活物蛋白和纤溶酶原激活物抑制剂1型蛋白的亚序列，以及可以在复合蛋白裂解物样品中直接测量这些肽的测定法，包括由组织学处理的福尔马林制备的蛋白质裂解物固定组织。来自受试者的样品中那些肽的存在和量可以与受试者中的疾病（包括癌症）相关，并提供关于疾病/癌症的诊断阶段/等级/状态的信息。

10. 发明申请

WO2012092532A3 PROTEIN BIOMARKERS OF LATE STAGE BREAST CANCER 审中-公开
公开(公告)号：WO2012092532A3
公开(公告)日：2012-07-05
申请号：PCT/US2011/068000
申请日：2011-12-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , DARFLER, Marlene, M. , CONRADS, Thomas, P. , HOOD, Brian, L. , BATEMAN, Nicholas, W.
发明人： KRIZMAN, David, B. , DARFLER, Marlene, M. , CONRADS, Thomas, P. , HOOD, Brian, L. , BATEMAN, Nicholas, W.
IPC分类号： G01N33/536
摘要： This patent application discloses and describes proteins found to be differentially expressed between primary tumor breast cancer cells histologicaly defined as early stage (stage 0) breast cancer and primary breast cancer cells histologicaly defined as late stage (stage 3) breast cancer. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from breast cancer patients to indicate the that a breast cancer patient's cancer is in an early, non- aggressive stage or in a late, aggressive stage. Determination of differential expression of these proteins can also be useful for indicating additional therapies to combat the aggressiveness of late stage breast cancer. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein the differentially expressed proteins that are used as diagnostic and prognostic indicators can also be used as targets for therapeutic intervention of breast cancer. Also disclosed and described herein are isotope labeled versions of peptides from the proteins.

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