Altered Plasma Apolipoprotein Modifications in Patients with Pancreatic Cancer: Protein Characterization and Multi-Institutional Validation
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{"title"=>"Altered Plasma Apolipoprotein Modifications in Patients with Pancreatic Cancer: Protein Characterization and Multi-Institutional Validation", "type"=>"journal", "authors"=>[{"first_name"=>"Kazufumi", "last_name"=>"Honda", "scopus_author_id"=>"26643336300"}, {"first_name"=>"Takuji", "last_name"=>"Okusaka", "scopus_author_id"=>"7003950274"}, {"first_name"=>"Klaus", "last_name"=>"Felix", "scopus_author_id"=>"7003656723"}, {"first_name"=>"Shoji", "last_name"=>"Nakamori", "scopus_author_id"=>"7103138387"}, {"first_name"=>"Naohiro", "last_name"=>"Sata", "scopus_author_id"=>"7005240763"}, {"first_name"=>"Hideo", "last_name"=>"Nagai", "scopus_author_id"=>"7403083981"}, {"first_name"=>"Tatsuya", "last_name"=>"Ioka", "scopus_author_id"=>"6603709682"}, {"first_name"=>"Akihiko", "last_name"=>"Tsuchida", "scopus_author_id"=>"7101698457"}, {"first_name"=>"Takeshi", "last_name"=>"Shimahara", "scopus_author_id"=>"23475061900"}, {"first_name"=>"Masashi", "last_name"=>"Shimahara", "scopus_author_id"=>"6701650892"}, {"first_name"=>"Yohichi", "last_name"=>"Yasunami", "scopus_author_id"=>"35369766300"}, {"first_name"=>"Hideya", "last_name"=>"Kuwabara", "scopus_author_id"=>"24781066400"}, {"first_name"=>"Tomohiro", "last_name"=>"Sakuma", "scopus_author_id"=>"24780914700"}, {"first_name"=>"Yoshihiko", "last_name"=>"Otsuka", "scopus_author_id"=>"55386200000"}, {"first_name"=>"Norihito", "last_name"=>"Ota", "scopus_author_id"=>"55385669000"}, {"first_name"=>"Miki", "last_name"=>"Shitashige", "scopus_author_id"=>"14047720300"}, {"first_name"=>"Tomoo", "last_name"=>"Kosuge", "scopus_author_id"=>"24526089600"}, {"first_name"=>"Markus W.", "last_name"=>"Büchler", "scopus_author_id"=>"55066608000"}, {"first_name"=>"Tesshi", "last_name"=>"Yamada", "scopus_author_id"=>"7405976374"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84867300937", "pmid"=>"23056525", "sgr"=>"84867300937", "doi"=>"10.1371/journal.pone.0046908", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"365821718"}, "id"=>"60495e18-826c-3465-803c-691c6a192446", "abstract"=>"BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.\\n\\nMETHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.\\n\\nRESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21), P = 4.35×10(-14), and P = 1.83×10(-24) (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a prospective cohort [Cohort 4 (n = 833)] collected from 8 medical institutions in Japan and Germany.\\n\\nCONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.", "link"=>"http://www.mendeley.com/research/altered-plasma-apolipoprotein-modifications-patients-pancreatic-cancer-protein-characterization-mult", "reader_count"=>14, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>5, "Business, Management and Accounting"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/563032"], "description"=>"<p>(<b>A and B</b>) ROC analysis of ApoAII-2, ApoCIII-0, and their combination (ApoAII-2+CIII-0) in Cohorts 1 (A) and 2 (B). (<b>C</b>) ROC analysis showing the capacity of ApoAII-2, ApoCIII-0, ApoAII-2+CIII-0, and CA19-9 for discrimination of pancreatic cancer patients from healthy controls in the German cohort (Cohort 3). (<b>D</b>) ROC analysis of ApoAII-2+CIII-0 in Cohort 4 according to clinical stage (Cohort 4). (<b>E</b>) Distribution of ApoAII-2+CIII-0 according to clinical stage. Lines indicate median values (Cohort 4).</p>", "links"=>[], "tags"=>["apoaii-2", "apociii-0", "pancreatic"], "article_id"=>233504, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduction_of_ApoAII_2_and_ApoCIII_0_in_pancreatic_cancer_/233504", "title"=>"Reduction of ApoAII-2 and ApoCIII-0 in pancreatic cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 00:58:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/563298"], "description"=>"<p>(<b>A and B</b>) Reactivity of anti-ApoAII (-ATQ) (<b>A</b>) and anti-ApoAII (-AT) (<b>B</b>) peptide antibodies with GST-tagged ApoAII monomers bearing -ATQ (GST-ATQ) (amino acids 1–100) and -AT (GST-AT) (amino acids 1–99) termini. (<b>C</b>) Non-denaturing immunoblot analysis of plasma samples from healthy controls (lanes a-f) and representative pancreatic cancer patients (lanes g-l) with antibodies against pan ApoAII protein (top), ApoAII (-ATQ) peptide (middle), and ApoAII (-ATQ) peptide (bottom). A pancreatic cancer patient (lane i) shows a slower-migrating ApoAII protein (indicated by ‡), but its molecular nature remains to be determined. (<b>D</b>) Gel-like image of oMALDI-QqTOF-MS spectra within the range 16,900–18,100 m/z for representative healthy controls (lanes a-f corresponding to <b>C</b>) and pancreatic cancer patients (lanes g-l corresponding to <b>C</b>).</p>", "links"=>[], "tags"=>["truncated", "apoaii"], "article_id"=>233770, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g006", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detection_of_truncated_ApoAII_peptide_/233770", "title"=>"Detection of truncated ApoAII peptide.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 01:02:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/562942"], "description"=>"<p>(<b>A</b>) Predicted three-dimensional structure of dimerized ApoAII protein. The model was built using the MOE software package (Ryoka Systems Inc., Tokyo, Japan). Red color indicates a disulfide bond. (<b>B</b>) Amino acid sequences and calculated theoretical molecular masses of ApoAII homo/heterodimers (ApoAII-1 to -5). Two peptides were dimerized via an N-terminal disulfide bond.</p>", "links"=>[], "tags"=>["apoaii"], "article_id"=>233419, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g003", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structure_of_ApoAII_dimers_/233419", "title"=>"Structure of ApoAII dimers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 00:56:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/563401"], "description"=>"a<p>Includes one case of unknown clinical stage. Positivity rates higher than 60% are highlighted in boldface.</p>", "links"=>[], "tags"=>["positivity", "rates", "gastrointestinal", "diseases"], "article_id"=>233869, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.t001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ApoAII_2_ApoCIII_0_positivity_rates_in_various_gastrointestinal_diseases_Cohort_4_/233869", "title"=>"ApoAII-2+ApoCIII-0 positivity rates in various gastrointestinal diseases (Cohort 4).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-10-08 01:04:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/300254", "https://ndownloader.figshare.com/files/300266", "https://ndownloader.figshare.com/files/300283", "https://ndownloader.figshare.com/files/300294", "https://ndownloader.figshare.com/files/300305", "https://ndownloader.figshare.com/files/300313", "https://ndownloader.figshare.com/files/300319", "https://ndownloader.figshare.com/files/300328", "https://ndownloader.figshare.com/files/300344", "https://ndownloader.figshare.com/files/300356", "https://ndownloader.figshare.com/files/300362", "https://ndownloader.figshare.com/files/300372"], "description"=>"<div><h3>Background</h3><p>Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.</p> <h3>Methods</h3><p>We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.</p> <h3>Results</h3><p>We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 <em>m/z</em>), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 <em>m/z</em>), and their summed value were significantly decreased in the pancreatic cancer patients [<em>P</em> = 1.36×10<sup>−21</sup>, <em>P</em> = 4.35×10<sup>−14</sup>, and <em>P</em> = 1.83×10<sup>−24</sup> (Mann-Whitney <em>U</em>-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (<em>n</em> = 103) and Cohort 3 (<em>n</em> = 163)] and a prospective cohort [Cohort 4 (<em>n</em> = 833)] collected from 8 medical institutions in Japan and Germany.</p> <h3>Conclusions</h3><p>We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.</p> </div>", "links"=>[], "tags"=>["altered", "plasma", "apolipoprotein", "modifications", "patients", "pancreatic", "characterization", "multi-institutional", "validation"], "article_id"=>119192, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046908.s001", "https://dx.doi.org/10.1371/journal.pone.0046908.s002", "https://dx.doi.org/10.1371/journal.pone.0046908.s003", "https://dx.doi.org/10.1371/journal.pone.0046908.s004", "https://dx.doi.org/10.1371/journal.pone.0046908.s005", "https://dx.doi.org/10.1371/journal.pone.0046908.s006", "https://dx.doi.org/10.1371/journal.pone.0046908.s007", "https://dx.doi.org/10.1371/journal.pone.0046908.s008", "https://dx.doi.org/10.1371/journal.pone.0046908.s009", "https://dx.doi.org/10.1371/journal.pone.0046908.s010", "https://dx.doi.org/10.1371/journal.pone.0046908.s011", "https://dx.doi.org/10.1371/journal.pone.0046908.s012"], "stats"=>{"downloads"=>25, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Altered_Plasma_Apolipoprotein_Modifications_in_Patients_with_Pancreatic_Cancer_Protein_Characterization_and_Multi_Institutional_Validation/119192", "title"=>"Altered Plasma Apolipoprotein Modifications in Patients with Pancreatic Cancer: Protein Characterization and Multi-Institutional Validation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-10-08 02:33:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/562830"], "description"=>"<p>(<b>A</b>) Spectra for representative pancreatic cancer patients and controls within the ranges 16,900 to 17,500 <i>m/z</i> (top) and 8500 to 9250 <i>m/z</i> (bottom). (<b>B</b>) Gel-like images of ApoAII and ApoCIII-0 in Cohort 1 (215 cases). (<b>A</b> and <b>B</b>) Black single asterisks (*), red double asterisks (**), black triple asterisks (***), and red quadruple asterisks (****) indicate MS peaks of ApoAII-1, ApoAII-2, ApoAII-3, and ApoCIII-0, respectively.</p>", "links"=>[], "tags"=>["profiling", "plasma"], "article_id"=>233305, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g002", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_oMALDI_QqTOF_MS_profiling_of_plasma_proteins_/233305", "title"=>"oMALDI-QqTOF-MS profiling of plasma proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 00:55:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/562730"], "description"=>"<p>(<b>A</b>) Two-dimensional plot analysis showing the correlation of 2173 corresponding peaks between two of the triplicate measurements (indicated in red, blue, and green) of a standard plasma mixture. Lines indicate 2-fold differences. (<b>B</b>) A standard plasma mixture was analyzed 24 times, and the CV values [ =  SD (bars)/mean (columns)] of representative protein peaks (ApoAI, ApoAII-2ox, ApoAII-2, and ApoCIII-0) were calculated. (<b>C</b>) Transition of CC values between the duplicate measurements of a standard plasma mixture in the 12 plates (24 measurements) of Cohort 1. (<b>D and E</b>) Correlation matrix (<b>D</b>) and distribution (<b>E</b>) of mutual similarity (CC values) for the 24 duplicate measurements (1–24).18.</p>", "links"=>[], "tags"=>["automated", "chromatography"], "article_id"=>233210, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reproducibility_of_automated_chromatography_and_oMALDI_QqTOF_MS_/233210", "title"=>"Reproducibility of automated chromatography and oMALDI-QqTOF-MS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 00:53:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/563189"], "description"=>"<p>Distribution (peak intensity in arbitrary units) (<b>A</b>), spectra of representative cases (<b>B</b>), and ROC analysis (<b>C</b>) of the indicated modified forms of ApoAII in Cohort 4. C, healthy control (<i>n</i> = 128); P, pancreatic cancer (<i>n</i> = 249).</p>", "links"=>[], "tags"=>["modification"], "article_id"=>233659, "categories"=>["Cancer", "Biochemistry", "Cell Biology"], "users"=>["Kazufumi Honda", "Takuji Okusaka", "Klaus Felix", "Shoji Nakamori", "Naohiro Sata", "Hideo Nagai", "Tatsuya Ioka", "Akihiko Tsuchida", "Takeshi Shimahara", "Masashi Shimahara", "Yohichi Yasunami", "Hideya Kuwabara", "Tomohiro Sakuma", "Yoshihiko Otsuka", "Norihito Ota", "Miki Shitashige", "Tomoo Kosuge", "Markus W. Büchler", "Tesshi Yamada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046908.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_modification_of_ApoAII_/233659", "title"=>"Differential modification of ApoAII.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-10-08 01:00:59"}

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Relative Metric

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