{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:22:54Z","timestamp":1790752974818,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA\/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label\u2010free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA\/Ps) and 17 normal colonic mucosa samples, archived as formalin\u2010fixed paraffin\u2010embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well\u2010individualized clusters composed of all the CADs (15\/15) and most of the SSA\/Ps (13\/17), respectively. This is consistent with the fact that CADs and SSA\/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA\/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal\/TGF\u03b2 pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA\/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA\/Ps or from normal mucosa evolving through a process related to the CAD pathway. \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5366","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:10:02Z","timestamp":1573776602000},"page":"251-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Proteome analysis of formalin\u2010fixed paraffin\u2010embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas"],"prefix":"10.1002","volume":"250","author":[{"given":"Pierre","family":"Sohier","sequence":"first","affiliation":[{"name":"Department of Pathology, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) H\u00f4pitaux Universitaires Paris Centre, H\u00f4pital Cochin Department  Paris France"},{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Sanson","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Leduc","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Plateforme de Prot\u00e9omique de l'Universit\u00e9 Paris Descartes (3P5)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Audebourg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) H\u00f4pitaux Universitaires Paris Centre, H\u00f4pital Cochin Department  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Broussard","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Plateforme de Prot\u00e9omique de l'Universit\u00e9 Paris Descartes (3P5)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Salnot","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Plateforme de Prot\u00e9omique de l'Universit\u00e9 Paris Descartes (3P5)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Alexandre","family":"Just","sequence":"additional","affiliation":[{"name":"Department of Pathology, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) H\u00f4pitaux Universitaires Paris Centre, H\u00f4pital Cochin Department  Paris France"},{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pasmant","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Department of Molecular Genetics, Assistance Publique\u2010H\u00f4pitaux de Paris H\u00f4pitaux Universitaires Paris Centre, Cochin Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Mayeux","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Plateforme de Prot\u00e9omique de l'Universit\u00e9 Paris Descartes (3P5)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Guillonneau","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"},{"name":"Plateforme de Prot\u00e9omique de l'Universit\u00e9 Paris Descartes (3P5)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Romagnolo","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-7051","authenticated-orcid":false,"given":"Christine","family":"Perret","sequence":"additional","affiliation":[{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Terris","sequence":"additional","affiliation":[{"name":"Department of Pathology, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) H\u00f4pitaux Universitaires Paris Centre, H\u00f4pital Cochin Department  Paris France"},{"name":"INSERM, U1016, Institut Cochin  Paris France"},{"name":"CNRS, UMR8104  Paris France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11252"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.066"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.73"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092317"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2010.05.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318157f002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-16-0081"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13688"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.064"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.037671"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02549.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.122"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.35"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.04.002"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.11.046"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4200"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088367"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-15-0363"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.050245"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1651562"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1322"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1511"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001453"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.145"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02466.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31821537a2"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29891"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1683-6"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2002.00528.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3992007cm1"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3750"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg732"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0105-4"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41559-018-0642-z"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.01.003"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05226-0"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.01.033"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06796-9"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.02.042"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0081-y"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093587"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-203593"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0650476"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.147"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw580"},{"key":"e_1_2_8_51_1","first-page":"100","article-title":"Optimal algorithm for metabolomics classification and feature selection varies by dataset","volume":"7","author":"Determan CE","year":"2015","journal-title":"Int J Biol"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:34:03Z","timestamp":1761050043000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,15]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/path.5366"],"URL":"https:\/\/doi.org\/10.1002\/path.5366","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,15]]},"assertion":[{"value":"2019-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}