{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:17:12Z","timestamp":1788347832897,"version":"build-2803163510"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T00:00:00Z","timestamp":1447372800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM49500"],"award-info":[{"award-number":["R01GM49500"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50CA130810"],"award-info":[{"award-number":["P50CA130810"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 154455"],"award-info":[{"award-number":["R01 154455"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Single amino acid variations are highly associated with many human diseases. The direct detection of peptides containing single amino acid variants (SAAVs) derived from nonsynonymous single nucleotide polymorphisms (SNPs) in serum can provide unique opportunities for SAAV associated biomarker discovery. In the present study, an isobaric labeling quantitative strategy was applied to identify and quantify variant peptides in serum samples of pancreatic cancer patients and other benign controls. The largest number of SAAV peptides to date in serum including 96 unique variant peptides were quantified in this quantitative analysis, of which five variant peptides showed a statistically significant difference between pancreatic cancer and other controls (p-value &amp;lt; 0.05). Significant differences in the variant peptide SDNCEDTPEAGYFAVAVVK from serotransferrin were detected between pancreatic cancer and controls, which was further validated by selected reaction monitoring (SRM) analysis. The novel biomarker panel obtained by combining \u03b1-1-antichymotrypsin (AACT), Thrombospondin-1 (THBS1) and this variant peptide showed an excellent diagnostic performance in discriminating pancreatic cancer from healthy controls (AUC = 0.98) and chronic pancreatitis (AUC = 0.90). These results suggest that large-scale analysis of SAAV peptides in serum may provide a new direction for biomarker discovery research.<\/jats:p>","DOI":"10.1021\/pr500934u","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T08:45:34Z","timestamp":1415868334000},"page":"6058-6066","source":"Crossref","is-referenced-by-count":29,"title":["Quantitative Analysis of Single\nAmino Acid Variant\nPeptides Associated with Pancreatic Cancer in Serum by an Isobaric\nLabeling Quantitative Method"],"prefix":"10.1021","volume":"13","author":[{"given":"Song","family":"Nie","sequence":"first","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidi","family":"Yin","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijing","family":"Tan","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mack T.","family":"Ruffin","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Simeone","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Lubman","sequence":"additional","affiliation":[{"name":"University of Michigan , , , ,","place":["Ann Arbor, Michigan, United States, 48109"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"issue":"7422","key":"2026090206574839600_cit1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated\nmap of genetic variation from 1,092 human genomes","volume":"491","author":"Abecasis","year":"2012","journal-title":"Nature"},{"issue":"3","key":"2026090206574839600_cit2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/10290","article-title":"Characterization of single-nucleotide polymorphisms\nin coding regions of human genes","volume":"22","author":"Cargill","year":"1999","journal-title":"Nat. Genet."},{"issue":"7145","key":"2026090206574839600_cit3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","volume":"447","year":"2007","journal-title":"Nature"},{"issue":"43","key":"2026090206574839600_cit4","doi-asserted-by":"crossref","first-page":"18545","DOI":"10.1073\/pnas.1010978107","article-title":"Accumulation of driver and passenger mutations during\ntumor progression","volume":"107","author":"Bozic","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S\nA."},{"issue":"7283","key":"2026090206574839600_cit5","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nature08768","article-title":"Signatures\nof mutation and selection in the cancer genome","volume":"463","author":"Bignell","year":"2010","journal-title":"Nature"},{"issue":"4","key":"2026090206574839600_cit6","first-page":"225","article-title":"Cancer statistics, 2009","volume":"59","author":"Jemal","year":"2009","journal-title":"CA Cancer\nJ. Clin."},{"issue":"3","key":"2026090206574839600_cit7","first-page":"203","article-title":"Identification and screening of individuals\nat increased risk for pancreatic cancer with emphasis on known environmental\nand genetic factors and hereditary syndromes","volume":"11","author":"Chu","year":"2010","journal-title":"J. Pncreas"},{"issue":"1","key":"2026090206574839600_cit8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1074\/mcp.M112.022996","article-title":"Putting the pieces together: High-performance LC-MS\/MS\nprovides network-, pathway-, and protein-level perspectives in populus","volume":"12","author":"Abraham","year":"2012","journal-title":"Mol. Cell Proteomics"},{"issue":"6","key":"2026090206574839600_cit9","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S1072-7515(99)00049-6","article-title":"Surgical palliation of unresectable periampullary adenocarcinoma\nin the 1990s","volume":"188","author":"Sohn","year":"1999","journal-title":"J. Am. Coll. Surg."},{"issue":"3","key":"2026090206574839600_cit10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00432-010-0965-x","article-title":"Serum biomarkers\nfor improved diagnostic of pancreatic cancer: a current overview","volume":"137","author":"Bunger","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"issue":"10","key":"2026090206574839600_cit11","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1158\/0008-5472.CAN-11-2883","article-title":"Identification of serum biomarker\nsignatures associated with pancreatic cancer","volume":"72","author":"Wingren","year":"2012","journal-title":"Cancer Res."},{"issue":"3","key":"2026090206574839600_cit12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/ng.522","article-title":"A genome-wide association\nstudy identifies pancreatic cancer susceptibility loci on chromosomes\n13q22.1, 1q32.1 and 5p15.33","volume":"42","author":"Petersen","year":"2010","journal-title":"Nat. Genet."},{"issue":"6","key":"2026090206574839600_cit13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nmeth0607-465","article-title":"A mass spectrometry-friendly database\nfor cSNP identification","volume":"4","author":"Schandorff","year":"2007","journal-title":"Nat. Methods"},{"issue":"5","key":"2026090206574839600_cit14","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/jmcb\/mjr024","article-title":"Quantitative\ndetection of single amino acid polymorphisms by targeted proteomics","volume":"3","author":"Su","year":"2011","journal-title":"J. Mol. Cell Biol."},{"issue":"1","key":"2026090206574839600_cit15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/scrt166","article-title":"Cancer stem cell contribution\nto glioblastoma invasiveness","volume":"4","author":"Ortensi","year":"2013","journal-title":"Stem Cell Res.\nTher."},{"issue":"1","key":"2026090206574839600_cit16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1021\/pr400544j","article-title":"Large-scale quantification of single amino-acid variations\nby a variation-associated\ndatabase search strategy","volume":"13","author":"Song","year":"2014","journal-title":"J. Proteome Res."},{"issue":"5","key":"2026090206574839600_cit17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/jmcb\/mju031","article-title":"De novo identification\nand quantification\nof single amino-acid variants in human brain","volume":"6","author":"Su","year":"2014","journal-title":"J. Mol. Cell Biol."},{"issue":"6","key":"2026090206574839600_cit18","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1073\/pnas.1019203108","article-title":"Mutant proteins\nas cancer-specific biomarkers","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"issue":"4","key":"2026090206574839600_cit19","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1021\/pr400967x","article-title":"Glycoprotein\nbiomarker panel for pancreatic cancer discovered by quantitative proteomics\nanalysis","volume":"13","author":"Nie","year":"2014","journal-title":"J. Proteome Res."},{"issue":"2","key":"2026090206574839600_cit20","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1021\/pr900715p","article-title":"Identification\nand confirmation of biomarkers using\nan integrated platform for quantitative analysis of glycoproteins\nand their glycosylations","volume":"9","author":"Liu","year":"2010","journal-title":"J. Proteome Res."},{"issue":"9","key":"2026090206574839600_cit21","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1021\/pr300330z","article-title":"Identification and\nconfirmation of differentially expressed\nfucosylated glycoproteins in the serum of ovarian cancer patients\nusing a lectin array and LC-MS\/MS","volume":"11","author":"Wu","year":"2012","journal-title":"J. Proteome\nRes."},{"issue":"11","key":"2026090206574839600_cit22","doi-asserted-by":"crossref","first-page":"5353","DOI":"10.1021\/ac400838s","article-title":"Isobaric\nprotein-level labeling strategy for serum glycoprotein quantification\nanalysis by liquid chromatography-tandem mass spectrometry","volume":"85","author":"Nie","year":"2013","journal-title":"Anal. Chem."},{"issue":"5","key":"2026090206574839600_cit23","doi-asserted-by":"crossref","first-page":"M110 006536","DOI":"10.1074\/mcp.M110.006536","article-title":"A bioinformatics workflow\nfor variant peptide detection in shotgun proteomics","volume":"10","author":"Li","year":"2011","journal-title":"Mol. Cell Proteomics"},{"issue":"8","key":"2026090206574839600_cit24","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1021\/pr400192r","article-title":"Moving away from\nthe reference genome: Evaluating a peptide sequencing tagging approach\nfor single amino acid polymorphism identifications in the genus Populus","volume":"12","author":"Abraham","year":"2013","journal-title":"J. Proteome Res."},{"key":"2026090206574839600_cit25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1134\/S1607672911020098","article-title":"Identification of\nsingle amino acid polymorphisms in MS\/MS spectra of peptides","volume":"437","author":"Chernobrovkin","year":"2010","journal-title":"Dokl. Biochem. Biophys."},{"issue":"1","key":"2026090206574839600_cit26","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1021\/pr4009207","article-title":"Large-scale\nmass spectrometric detection of variant peptides resulting from nonsynonymous\nnucleotide differences","volume":"13","author":"Sheynkman","year":"2014","journal-title":"J. Proteome Res."},{"issue":"1","key":"2026090206574839600_cit27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1021\/pr400544j","article-title":"Large-scale quantification of single amino-Acid variations\nby a variation-associated\ndatabase search strategy","volume":"13","author":"Song","year":"2014","journal-title":"J. Proteome Res."},{"key":"2026090206574839600_cit28","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/msb.2008.61","article-title":"Selected reaction\nmonitoring for quantitative proteomics: a tutorial","volume":"4","author":"Lange","year":"2008","journal-title":"Mol. Syst. Biol."},{"key":"2026090206574839600_cit29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jprot.2014.04.018","article-title":"PeptidePicker:\nA scientific workflow\nwith web interface for selecting appropriate peptides for targeted\nproteomics experiments","volume":"106","author":"Mohammed","year":"2014","journal-title":"J. Proteomics"},{"issue":"1","key":"2026090206574839600_cit30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1021\/pr300893w","article-title":"Standardized protocols\nfor quality control of MRM-based plasma proteomic workflows","volume":"12","author":"Percy","year":"2012","journal-title":"J. Proteome Res."},{"key":"2026090206574839600_cit31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jprot.2013.07.026","article-title":"Method and platform\nstandardization in MRM-based quantitative plasma proteomics","volume":"95","author":"Percy","year":"2013","journal-title":"J. Proteomics"},{"issue":"9","key":"2026090206574839600_cit32","doi-asserted-by":"crossref","first-page":"704","DOI":"10.7326\/0003-4819-110-9-704","article-title":"Evaluation of a serologic marker, CA19\u20139, in\nthe diagnosis of pancreatic cancer","volume":"110","author":"Pleskow","year":"1989","journal-title":"Ann. Int.\nMed."}],"container-title":["Journal of\nProteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr500934u","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/12\/6058\/13538219\/pr500934u.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/12\/6058\/13538219\/pr500934u.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:58:09Z","timestamp":1788346689000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/13\/12\/6058\/1339560\/Quantitative-Analysis-of-Single-Amino-Acid-Variant"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,13]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,11,13]]},"published-print":{"date-parts":[[2014,12,5]]}},"URL":"https:\/\/doi.org\/10.1021\/pr500934u","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,13]]}}}