{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T21:29:48Z","timestamp":1784064588099,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Panitumumab shows limited clinical benefit in colorectal cancer (CRC), and reliable predictive biomarkers to guide patient selection remain lacking. To address this gap, we investigated molecular determinants of therapeutic response using tumor samples from patients with primary and metastatic CRC. By integrating PIMS\u2010based metastatic classification, NPOT interaction profiling and quantitative proteomics, this study aimed to identify response\u2010associated pathways and potential prognostic biomarkers that could support improved stratification for panitumumab therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010one tumor resection samples from twenty CRC patients from primary site (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) and from intrahepatic metastasis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099), female (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) and male (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914) were analyzed. Clinical metadata of donors was associated with molecular properties of each sample. Patients\u2019 cryostored tumor material was blinded before subjecting to PIMS analysis. PIMS analysis was at first performed to separate metastatic and non\u2010metastatic patients. After uncovering the blind, tumors were all challenged by 1 \u03bcg of panitumumab in PIMS to identify responder and non\u2010responder with or without metastasis. Tumors from metastatic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) and non\u2010metastatic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092) patients were thereafter analyzed by NPOT to identify EGFR\u2010related signaling pathway. All group tumors were analyzed using label\u2010free quantitative proteomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PIMS identified with 82% accuracy metastatic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) from non\u2010metastatic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) tumor. The metastatic tumor had higher resonance volumes (2948\u20135094) compared to non\u2010metastatic (1076\u20132759) tumor. NPOT identified EGFR only in metastatic tumor. The metastatic interactome was composed of 34 proteins (EGFR, PTPN1, CTNNB1, CTNND1, YWHAZ, CD44, FN1, ITGB1, GADPH, ENO1, HSPA4, HSPA8, HSP90AA1, HSP90AB1, ANXA2, A1BG, DNTM1, TSR1, RPS27, PPM1G, SMC2, LIG1, NCAPD2, POLD1, PRKDC, YBX1, ANK1, FTL, NCL, ITGB2, SERPINA7, HP, and A2M). The first 10 proteins (underlined) were shared also with non\u2010metastatic tumors. Label\u2010free quantitative proteomics identified 145 differentiated protein, 15 of which were enriched and 130 impoverished specifically in metastatic tumors. Evidence suggests that HSPA4, HSP90AB1, DNTM1, RPS27, FTL, NCL, A2M are implicated in the pathogenesis and progression of colorectal cancer, positioning them as potential prognostic biomarkers for the onset of metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combination of PIMS and NPOT coupled to label\u2010free quantitative proteomics point towards the distinct panitumumab mode of action in CRC patients and highlights specific proteins as prognostic biomarkers which need further validation in a bigger cohort and multicentric investigation, ideally involving patient registry follow up data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Novelty and Impact<\/jats:title>\n                    <jats:p>This study presents an integrative molecular profiling strategy that combines PIMS, NPOT, and proteomics to uncover mechanistically relevant biomarkers of therapeutic response in colorectal cancer. By identifying an EGFR\u2010centered interactome and responder\u2010specific protein signatures, the research offers a novel approach to stratify panitumumab response and supports advancement of precision oncology in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71387","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:41:53Z","timestamp":1764506513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Resonance Quantification and Label\u2010Free Interactome Characterization of Total Proteome of Tumor Specimens Decipher Responder and Success Predictors in Colorectal Cancer Patients Treated With Panitumumab"],"prefix":"10.1002","volume":"14","author":[{"given":"Angelique","family":"Quartier","sequence":"first","affiliation":[{"name":"Inoviem Scientific  Illkirch Graffenstaden France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7786-2200","authenticated-orcid":false,"given":"Ahmed Y.","family":"Sanin","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Nagelschmitz","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Schneider","sequence":"additional","affiliation":[{"name":"Inoviem Scientific  Illkirch Graffenstaden France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7345-579X","authenticated-orcid":false,"given":"Wenjie","family":"Shi","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wartmann","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"D\u00f6lling","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederike","family":"Stelter","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihailo","family":"Andric","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland S.","family":"Croner","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"},{"name":"Research Campus STIMULATE Otto von Guericke University Magdeburg  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Eftekhari","sequence":"additional","affiliation":[{"name":"Inoviem Scientific  Illkirch Graffenstaden France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf D.","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Surgery, University Clinic for General, Visceral, Vascular and Transplantation Surgery, Medical Faculty University Hospital Magdeburg Otto\u2010von Guericke University  Magdeburg Germany"},{"name":"Research Campus STIMULATE Otto von Guericke University Magdeburg  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"257","article-title":"Exploring the Potential of Epiregulin and Amphiregulin as Prognostic, Predictive, and Therapeutic Targets in Colorectal Cancer","volume":"4","author":"Guernsey\u2010Biddle C.","year":"2024","journal-title":"Oncologist"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113854"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112748"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.32604\/or.2025.059311"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000358151"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otaa037"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29281-1"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22151"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24900-3"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1992481"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409630102"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.3253299"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1806402"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.03.026"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2141-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.10735"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2015.05.019"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.569"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgz181"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.803244"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.139345"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8060532"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104342"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz134"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71387","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.71387","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:27:27Z","timestamp":1771331247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,30]]},"references-count":24,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cam4.71387"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71387","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,30]]},"assertion":[{"value":"2025-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71387"}}