Haptoglobin-α subunit as potential Serum biomarker in ovarian cancer: Identification and characterization Using proteomic profiling and mass spectrometry
The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and...
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| Veröffentlicht in: | Clinical cancer research 2003-08, Vol.9 (8), p.2904-2911 |
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| creator | BIN YE CRAMER, Daniel W MOK, Samuel C SKATES, Steven J GYGI, Steven P PRATOMO, Vanessa LANFEI FU HORICK, Nora K LICKLIDER, Larry J SCHORGE, John O BERKOWITZ, Ross S |
| description | The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays.
Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens.
Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was |
| format | Article |
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Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens.
Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was </=2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125.
Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 12912935</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Amino Acid Sequence ; Biological and medical sciences ; Biomarkers, Tumor - blood ; Biotin - metabolism ; Blotting, Western ; CA-125 Antigen - blood ; Dimerization ; Enzyme-Linked Immunosorbent Assay ; Female ; Female genital diseases ; Genital Neoplasms, Female - blood ; Gynecology. Andrology. Obstetrics ; Haptoglobins - biosynthesis ; Humans ; Mass Spectrometry ; Medical sciences ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms - blood ; Ovarian Neoplasms - diagnosis ; Peptides - chemistry ; Proteomics - methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Time Factors ; Tumors</subject><ispartof>Clinical cancer research, 2003-08, Vol.9 (8), p.2904-2911</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15034350$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12912935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BIN YE</creatorcontrib><creatorcontrib>CRAMER, Daniel W</creatorcontrib><creatorcontrib>MOK, Samuel C</creatorcontrib><creatorcontrib>SKATES, Steven J</creatorcontrib><creatorcontrib>GYGI, Steven P</creatorcontrib><creatorcontrib>PRATOMO, Vanessa</creatorcontrib><creatorcontrib>LANFEI FU</creatorcontrib><creatorcontrib>HORICK, Nora K</creatorcontrib><creatorcontrib>LICKLIDER, Larry J</creatorcontrib><creatorcontrib>SCHORGE, John O</creatorcontrib><creatorcontrib>BERKOWITZ, Ross S</creatorcontrib><title>Haptoglobin-α subunit as potential Serum biomarker in ovarian cancer: Identification and characterization Using proteomic profiling and mass spectrometry</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays.
Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens.
Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was </=2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125.
Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies.</description><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biotin - metabolism</subject><subject>Blotting, Western</subject><subject>CA-125 Antigen - blood</subject><subject>Dimerization</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Genital Neoplasms, Female - blood</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Haptoglobins - biosynthesis</subject><subject>Humans</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Ovarian Neoplasms - blood</subject><subject>Ovarian Neoplasms - diagnosis</subject><subject>Peptides - chemistry</subject><subject>Proteomics - methods</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Time Factors</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkN9KwzAUxosobk5fQXKjd4U0f9rOOxnqBgMvdNflJE1ntE1qkgrzUXwLX8RnMmUT4cA5fPz4-M53lEwzzouUkpwfxxsXZYoZJZPkzPtXjDOWYXaaTDIyj0P5NPlaQh_strVCm_TnG_lBDEYHBB71NigTNLToSbmhQ0LbDtybckgbZD_AaTBIgpHK3aBVPbKNlhC0NQhMjeQLOJBBOf25Fzdemy3qXfS1nZbj1eh21Ea8A--R75UMznYquN15ctJA69XFYc-Szf3d82KZrh8fVovbddoTOg8pYULh-GiTk5LWeckoV6wpsKAF5RTn83nelBJEk5GyUCwjrKSqzkqOscAFI3SWXO99Y573QflQddpL1bZglB18FW0YZZhH8PIADqJTddU7HQvZVX9tRuDqAICX0DYulqP9P8cxjekw_QVPQII1</recordid><startdate>20030801</startdate><enddate>20030801</enddate><creator>BIN YE</creator><creator>CRAMER, Daniel W</creator><creator>MOK, Samuel C</creator><creator>SKATES, Steven J</creator><creator>GYGI, Steven P</creator><creator>PRATOMO, Vanessa</creator><creator>LANFEI FU</creator><creator>HORICK, Nora K</creator><creator>LICKLIDER, Larry J</creator><creator>SCHORGE, John O</creator><creator>BERKOWITZ, Ross S</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030801</creationdate><title>Haptoglobin-α subunit as potential Serum biomarker in ovarian cancer: Identification and characterization Using proteomic profiling and mass spectrometry</title><author>BIN YE ; CRAMER, Daniel W ; MOK, Samuel C ; SKATES, Steven J ; GYGI, Steven P ; PRATOMO, Vanessa ; LANFEI FU ; HORICK, Nora K ; LICKLIDER, Larry J ; SCHORGE, John O ; BERKOWITZ, Ross S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p239t-24be0078f6283d68435e4f70b3735306996f8cabf1287e412483ed18500b07423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biotin - metabolism</topic><topic>Blotting, Western</topic><topic>CA-125 Antigen - blood</topic><topic>Dimerization</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Genital Neoplasms, Female - blood</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Haptoglobins - biosynthesis</topic><topic>Humans</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Ovarian Neoplasms - blood</topic><topic>Ovarian Neoplasms - diagnosis</topic><topic>Peptides - chemistry</topic><topic>Proteomics - methods</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Time Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BIN YE</creatorcontrib><creatorcontrib>CRAMER, Daniel W</creatorcontrib><creatorcontrib>MOK, Samuel C</creatorcontrib><creatorcontrib>SKATES, Steven J</creatorcontrib><creatorcontrib>GYGI, Steven P</creatorcontrib><creatorcontrib>PRATOMO, Vanessa</creatorcontrib><creatorcontrib>LANFEI FU</creatorcontrib><creatorcontrib>HORICK, Nora K</creatorcontrib><creatorcontrib>LICKLIDER, Larry J</creatorcontrib><creatorcontrib>SCHORGE, John O</creatorcontrib><creatorcontrib>BERKOWITZ, Ross S</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BIN YE</au><au>CRAMER, Daniel W</au><au>MOK, Samuel C</au><au>SKATES, Steven J</au><au>GYGI, Steven P</au><au>PRATOMO, Vanessa</au><au>LANFEI FU</au><au>HORICK, Nora K</au><au>LICKLIDER, Larry J</au><au>SCHORGE, John O</au><au>BERKOWITZ, Ross S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Haptoglobin-α subunit as potential Serum biomarker in ovarian cancer: Identification and characterization Using proteomic profiling and mass spectrometry</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2003-08-01</date><risdate>2003</risdate><volume>9</volume><issue>8</issue><spage>2904</spage><epage>2911</epage><pages>2904-2911</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays.
Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens.
Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was </=2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125.
Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12912935</pmid><tpages>8</tpages></addata></record> |
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| subjects | Amino Acid Sequence Biological and medical sciences Biomarkers, Tumor - blood Biotin - metabolism Blotting, Western CA-125 Antigen - blood Dimerization Enzyme-Linked Immunosorbent Assay Female Female genital diseases Genital Neoplasms, Female - blood Gynecology. Andrology. Obstetrics Haptoglobins - biosynthesis Humans Mass Spectrometry Medical sciences Molecular Sequence Data Oligonucleotide Array Sequence Analysis Ovarian Neoplasms - blood Ovarian Neoplasms - diagnosis Peptides - chemistry Proteomics - methods Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Time Factors Tumors |
| title | Haptoglobin-α subunit as potential Serum biomarker in ovarian cancer: Identification and characterization Using proteomic profiling and mass spectrometry |
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