Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray
The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer. Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry...
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| Veröffentlicht in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2011-10, Vol.20 (10), p.2195-2203 |
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| creator | MATSUBARA, Junichi HONDA, Kazufumi NAGAI, Hideo LOKA, Tatsuya OKUSAKA, Takuji KOSUGE, Tomoo TSUCHIDA, Akihiko SHIMAHARA, Masashi YASUNAMI, Yohichi CHIBA, Tsutomu YAMADA, Tesshi ONO, Masaya SEKINE, Shigeki TANAKA, Yoshinori KOBAYASHI, Michimoto GIMAN JUNG SAKUMA, Tomohiro NAKAMORI, Shoji SATA, Naohiro |
| description | The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.
Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.
From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.
Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.
The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies. |
| doi_str_mv | 10.1158/1055-9965.epi-11-0400 |
| format | Article |
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Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.
From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.
Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.
The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies.</description><identifier>ISSN: 1055-9965</identifier><identifier>EISSN: 1538-7755</identifier><identifier>DOI: 10.1158/1055-9965.epi-11-0400</identifier><identifier>PMID: 21828233</identifier><identifier>CODEN: CEBPE4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Area Under Curve ; Biological and medical sciences ; biomarkers ; Biomarkers, Tumor - blood ; Blood Proteins - metabolism ; Blotting, Western ; Case-Control Studies ; Chromatography, Liquid ; Colorectal cancer ; Colorectal Neoplasms - metabolism ; Electrophoresis, Gel, Two-Dimensional ; Female ; Fibers ; Follow-Up Studies ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Image processing ; Immunoenzyme Techniques ; Intestine ; Liquid chromatography ; Male ; Mass spectroscopy ; Medical sciences ; Membrane Proteins - metabolism ; Middle Aged ; Neoplasm Staging ; Perilipin-2 ; Plasma proteins ; Prognosis ; Prospective Studies ; Protein Array Analysis ; Protein arrays ; Proteome - analysis ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tandem Mass Spectrometry ; Tumors</subject><ispartof>Cancer epidemiology, biomarkers & prevention, 2011-10, Vol.20 (10), p.2195-2203</ispartof><rights>2015 INIST-CNRS</rights><rights>2011 AACR</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c580t-748dcad28d845b641d4748fea6b409fdbd76b34f66170ad34cf93e8dddaed79d3</citedby><cites>FETCH-LOGICAL-c580t-748dcad28d845b641d4748fea6b409fdbd76b34f66170ad34cf93e8dddaed79d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24611830$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21828233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MATSUBARA, Junichi</creatorcontrib><creatorcontrib>HONDA, Kazufumi</creatorcontrib><creatorcontrib>NAGAI, Hideo</creatorcontrib><creatorcontrib>LOKA, Tatsuya</creatorcontrib><creatorcontrib>OKUSAKA, Takuji</creatorcontrib><creatorcontrib>KOSUGE, Tomoo</creatorcontrib><creatorcontrib>TSUCHIDA, Akihiko</creatorcontrib><creatorcontrib>SHIMAHARA, Masashi</creatorcontrib><creatorcontrib>YASUNAMI, Yohichi</creatorcontrib><creatorcontrib>CHIBA, Tsutomu</creatorcontrib><creatorcontrib>YAMADA, Tesshi</creatorcontrib><creatorcontrib>ONO, Masaya</creatorcontrib><creatorcontrib>SEKINE, Shigeki</creatorcontrib><creatorcontrib>TANAKA, Yoshinori</creatorcontrib><creatorcontrib>KOBAYASHI, Michimoto</creatorcontrib><creatorcontrib>GIMAN JUNG</creatorcontrib><creatorcontrib>SAKUMA, Tomohiro</creatorcontrib><creatorcontrib>NAKAMORI, Shoji</creatorcontrib><creatorcontrib>SATA, Naohiro</creatorcontrib><title>Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray</title><title>Cancer epidemiology, biomarkers & prevention</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.
Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.
From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.
Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.
The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies.</description><subject>Adult</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Blood Proteins - metabolism</subject><subject>Blotting, Western</subject><subject>Case-Control Studies</subject><subject>Chromatography, Liquid</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Electrophoresis, Gel, Two-Dimensional</subject><subject>Female</subject><subject>Fibers</subject><subject>Follow-Up Studies</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Image processing</subject><subject>Immunoenzyme Techniques</subject><subject>Intestine</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Medical sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Perilipin-2</subject><subject>Plasma proteins</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Protein Array Analysis</subject><subject>Protein arrays</subject><subject>Proteome - analysis</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tandem Mass Spectrometry</subject><subject>Tumors</subject><issn>1055-9965</issn><issn>1538-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhS1ERR_wE0DeILpJseNHnGUZtTDSVAyCrq0bP8CQxKmdqTR_pb8WR53Critbx9-5R74HobeUXFAq1EdKhKjaVooLN4WK0opwQl6gEyqYqppGiJfl_sQco9OcfxNCmlaIV-i4pqpWNWMn6GFt3TgHHwzMIY44enxpwxSnX6EPI4aMAW_jvDDQ420PeQD8KcQB0h-XsI8Jr2IfkzNzeV_BaIp6m8P4E2-gc311nZzD33ZQBswl4t7hG8gZf5-KI8XBzWmPYbR4m0pKSbwJJkVICfav0ZGHPrs3h_MM3V5f_Vh9qTZfP69Xl5vKCEXmquHKGrC1soqLTnJqeZG8A9lx0nrb2UZ2jHspaUPAMm58y5yy1oKzTWvZGfrwOHdK8W7n8qyHkI3rexhd3GWtWqlYLQQt5PmzJK2ZojVlTBZUPKLlNzkn5_WUQlnaXlOilwL1Uo5eytFX23WR9FJg8b07ROy6wdl_rqfGCvD-AEA20PtUVh7yf45LShUj7C9_Oqcc</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>MATSUBARA, Junichi</creator><creator>HONDA, Kazufumi</creator><creator>NAGAI, Hideo</creator><creator>LOKA, Tatsuya</creator><creator>OKUSAKA, Takuji</creator><creator>KOSUGE, Tomoo</creator><creator>TSUCHIDA, Akihiko</creator><creator>SHIMAHARA, Masashi</creator><creator>YASUNAMI, Yohichi</creator><creator>CHIBA, Tsutomu</creator><creator>YAMADA, Tesshi</creator><creator>ONO, Masaya</creator><creator>SEKINE, Shigeki</creator><creator>TANAKA, Yoshinori</creator><creator>KOBAYASHI, Michimoto</creator><creator>GIMAN JUNG</creator><creator>SAKUMA, Tomohiro</creator><creator>NAKAMORI, Shoji</creator><creator>SATA, Naohiro</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>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20111001</creationdate><title>Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray</title><author>MATSUBARA, Junichi ; HONDA, Kazufumi ; NAGAI, Hideo ; LOKA, Tatsuya ; OKUSAKA, Takuji ; KOSUGE, Tomoo ; TSUCHIDA, Akihiko ; SHIMAHARA, Masashi ; YASUNAMI, Yohichi ; CHIBA, Tsutomu ; YAMADA, Tesshi ; ONO, Masaya ; SEKINE, Shigeki ; TANAKA, Yoshinori ; KOBAYASHI, Michimoto ; GIMAN JUNG ; SAKUMA, Tomohiro ; NAKAMORI, Shoji ; SATA, Naohiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c580t-748dcad28d845b641d4748fea6b409fdbd76b34f66170ad34cf93e8dddaed79d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Blood Proteins - metabolism</topic><topic>Blotting, Western</topic><topic>Case-Control Studies</topic><topic>Chromatography, Liquid</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Electrophoresis, Gel, Two-Dimensional</topic><topic>Female</topic><topic>Fibers</topic><topic>Follow-Up Studies</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Image processing</topic><topic>Immunoenzyme Techniques</topic><topic>Intestine</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Medical sciences</topic><topic>Membrane Proteins - metabolism</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Perilipin-2</topic><topic>Plasma proteins</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Protein Array Analysis</topic><topic>Protein arrays</topic><topic>Proteome - analysis</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tandem Mass Spectrometry</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MATSUBARA, Junichi</creatorcontrib><creatorcontrib>HONDA, Kazufumi</creatorcontrib><creatorcontrib>NAGAI, Hideo</creatorcontrib><creatorcontrib>LOKA, Tatsuya</creatorcontrib><creatorcontrib>OKUSAKA, Takuji</creatorcontrib><creatorcontrib>KOSUGE, Tomoo</creatorcontrib><creatorcontrib>TSUCHIDA, Akihiko</creatorcontrib><creatorcontrib>SHIMAHARA, Masashi</creatorcontrib><creatorcontrib>YASUNAMI, Yohichi</creatorcontrib><creatorcontrib>CHIBA, Tsutomu</creatorcontrib><creatorcontrib>YAMADA, Tesshi</creatorcontrib><creatorcontrib>ONO, Masaya</creatorcontrib><creatorcontrib>SEKINE, Shigeki</creatorcontrib><creatorcontrib>TANAKA, Yoshinori</creatorcontrib><creatorcontrib>KOBAYASHI, Michimoto</creatorcontrib><creatorcontrib>GIMAN JUNG</creatorcontrib><creatorcontrib>SAKUMA, Tomohiro</creatorcontrib><creatorcontrib>NAKAMORI, Shoji</creatorcontrib><creatorcontrib>SATA, Naohiro</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>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MATSUBARA, Junichi</au><au>HONDA, Kazufumi</au><au>NAGAI, Hideo</au><au>LOKA, Tatsuya</au><au>OKUSAKA, Takuji</au><au>KOSUGE, Tomoo</au><au>TSUCHIDA, Akihiko</au><au>SHIMAHARA, Masashi</au><au>YASUNAMI, Yohichi</au><au>CHIBA, Tsutomu</au><au>YAMADA, Tesshi</au><au>ONO, Masaya</au><au>SEKINE, Shigeki</au><au>TANAKA, Yoshinori</au><au>KOBAYASHI, Michimoto</au><au>GIMAN JUNG</au><au>SAKUMA, Tomohiro</au><au>NAKAMORI, Shoji</au><au>SATA, Naohiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray</atitle><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>20</volume><issue>10</issue><spage>2195</spage><epage>2203</epage><pages>2195-2203</pages><issn>1055-9965</issn><eissn>1538-7755</eissn><coden>CEBPE4</coden><abstract>The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.
Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.
From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.
Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.
The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>21828233</pmid><doi>10.1158/1055-9965.epi-11-0400</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer epidemiology, biomarkers & prevention, 2011-10, Vol.20 (10), p.2195-2203 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Area Under Curve Biological and medical sciences biomarkers Biomarkers, Tumor - blood Blood Proteins - metabolism Blotting, Western Case-Control Studies Chromatography, Liquid Colorectal cancer Colorectal Neoplasms - metabolism Electrophoresis, Gel, Two-Dimensional Female Fibers Follow-Up Studies Gastroenterology. Liver. Pancreas. Abdomen Humans Image processing Immunoenzyme Techniques Intestine Liquid chromatography Male Mass spectroscopy Medical sciences Membrane Proteins - metabolism Middle Aged Neoplasm Staging Perilipin-2 Plasma proteins Prognosis Prospective Studies Protein Array Analysis Protein arrays Proteome - analysis Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tandem Mass Spectrometry Tumors |
| title | Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray |
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