{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:21:59Z","timestamp":1772137319069,"version":"3.50.1"},"reference-count":42,"publisher":"Proceedings of the National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,2,22]]},"abstract":"<jats:p>\n                    A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (\n                    <jats:italic>PTEN<\/jats:italic>\n                    ) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775\n                    <jats:italic>N<\/jats:italic>\n                    -linked glycoproteins from sera and prostate tissue of wild-type and\n                    <jats:italic>Pten<\/jats:italic>\n                    -null mice. Using label-free quantitative proteomics, we showed that\n                    <jats:italic>Pten<\/jats:italic>\n                    inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue\n                    <jats:italic>PTEN<\/jats:italic>\n                    status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1013699108","type":"journal-article","created":{"date-parts":[[2011,2,8]],"date-time":"2011-02-08T00:35:23Z","timestamp":1297125323000},"page":"3342-3347","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer"],"prefix":"10.1073","volume":"108","author":[{"given":"Igor","family":"Cima","sequence":"first","affiliation":[{"name":"Institute of Cell Biology and"}]},{"given":"Ralph","family":"Schiess","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland;"}]},{"given":"Peter","family":"Wild","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"}]},{"given":"Martin","family":"Kaelin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}]},{"given":"Peter","family":"Sch\u00fcffler","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Eidgen\u00f6ssische Technische Hochschule Zurich, 8092 Zurich, Switzerland; and"}]},{"given":"Vinzenz","family":"Lange","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland;"}]},{"given":"Paola","family":"Picotti","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland;"}]},{"given":"Reto","family":"Ossola","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland;"}]},{"given":"Arnoud","family":"Templeton","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}]},{"given":"Olga","family":"Schubert","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and"}]},{"given":"Thomas","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Eidgen\u00f6ssische Technische Hochschule Zurich, 8092 Zurich, Switzerland; and"}]},{"given":"Thomas","family":"Leippold","sequence":"additional","affiliation":[{"name":"Department of Urology, and"}]},{"given":"Stephen","family":"Wyler","sequence":"additional","affiliation":[{"name":"Department of Urology, and"}]},{"given":"Jens","family":"Zehetner","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and"}]},{"given":"Wolfram","family":"Jochum","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland;"}]},{"given":"Joachim","family":"Buhmann","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Eidgen\u00f6ssische Technische Hochschule Zurich, 8092 Zurich, Switzerland; and"}]},{"given":"Thomas","family":"Cerny","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}]},{"given":"Holger","family":"Moch","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"}]},{"given":"Silke","family":"Gillessen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology,"}]},{"given":"Ruedi","family":"Aebersold","sequence":"additional","affiliation":[{"name":"Institute of Molecular Systems Biology, Eidgen\u00f6ssische Technische Hochschule Zurich, 8093 Zurich, Switzerland;"},{"name":"Faculty of Science, University of Zurich, 8057 Zurich, Switzerland"}]},{"given":"Wilhelm","family":"Krek","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and"}]}],"member":"341","published-online":{"date-parts":[[2011,2,7]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"176","article-title":"Genomic and proteomic biomarkers for cancer: A multitude of opportunities","volume":"1796","author":"Tainsky MA","year":"2009","unstructured":"MA Tainsky, Genomic and proteomic biomarkers for cancer: A multitude of opportunities. Biochim Biophys Acta 1796, 176\u2013193 (2009).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1739"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(01)00560-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1235"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-356"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13375"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81780-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609139104"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0000059"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M600160-MCP200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2008.12.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt827"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.131"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr000423j"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700057"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac0498563"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510652103"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702507104"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2559"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2006.04.003"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1546"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2008.61"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-4541-9"},{"key":"e_1_3_3_25_2","first-page":"4291","article-title":"Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage","volume":"59","author":"McMenamin ME","year":"1999","unstructured":"ME McMenamin, et al., Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 59, 4291\u20134296 (1999).","journal-title":"Cancer Res"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-004-1004-6"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.01.013"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07762"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.02.028"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810084"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810696"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00763-6"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1550"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61085-0"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2664"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2926"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0125"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1031"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800172-MCP200"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012025199"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0832254100"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0798-844"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1013699108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:28:03Z","timestamp":1649791683000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1013699108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,7]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,2,22]]}},"alternative-id":["10.1073\/pnas.1013699108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1013699108","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.8693961.11936054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,7]]},"assertion":[{"value":"2011-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}