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Hillebrandt"],"technology_type":["Mass Spectrometry","Bottom-up proteomics"],"software":["Not available"],"submitter_keywords":["Human","crc","Human; crlm; crc","crlm"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD065812"],"tissue":["Colorectal Cancer Cell"],"sample_protocol":["Protein identification was performed using a nano-liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS) approach as previously described by Wisniewksi et al. (2009).[14] All samples were lyophilized, homogenized, and prepared for LC/MS using the Filter-Aided Sample Preparation (FASP) method, involving the injection of 4 µl of eluate into a nanoUHPLC system (Dionex UltiMate 3000, Thermo Fisher Scientific, Waltham, MA, USA) coupled with an timsTOF HT flex mass spectrometer (Bruker Daltonics) equipped with a CaptiveSpray nano-electrospray ion source 2 (timsTOF flex HT, Bruker Daltonic GmbH, Bremen, Germany).[14] Spectra libraries were created with pool samples by data in data dependent analyses (DDA). Parallel accumulation-serial fragmentation combined with data-independent acquisition (diaPASEF) was performed.[15] Spectra library was used to search against the acquired diaPASEF raw data files via PEAKS studio proteomics search engine (Version 11.5 Bioinformatics Solutions, Waterloo, Canada). Label-free quantification (LFQ) with PEAKS Q was used, whereby PEAKS was allowed to autodetect the reference sample and automatically align the sample runs. To facilitate the export of complete results, the protein significance filter was set to 0, the protein fold change filter to 1, and unique peptide filter to 1 in the export settings."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["A qualitative analysis first aimed to ensure robustness by establishing presence criteria for subgroup analysis: (a) unique-peptide-to-peptide ratio (UPR) ≥ 0.2, (b) unique peptide count (UPC) ≥ 2, and (c) coverage ≥ 5 in at least 75% of patients per subgroup. Proteins were included in downstream analysis if classified as \"present\" in at least one of the compared groups."],"omics_type":["Proteomics"],"labhead":["Karl Hillebrandt"],"instrument_platform":[""],"labhead_affiliation":["Charité Univeristätsmedizin Berlin, Department of Surgery, Augustenburger Platz 1, 13353 Berlin"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"publication":["41787508 Böhm AK, Skrip LM, Klein O, Strobl F, Wieland JK, Arnold A, Zhou Y, Papke B, Sers C, Modest DP, Moosburner S, Haber PK, Krenzien F, Raschzok N, Schöning W, Horst D, Malinka T, Sack I, Pratschke J, Sauer IM, Hillebrandt KH. Proteomic profiling of colorectal liver metastases reveals histopathological response-specific molecular signatures of chemotherapy efficacy. J Transl Med. 2026 24(1):487 10.1186/s12967-026-07945-1"],"submitter_mail":["karl-herbert.hillebrandt@charite.de"],"submitter_affiliation":["Department of Surgery"],"submitter_country":["Germany"],"pubmed_title":["Proteomic profiling of colorectal liver metastases reveals histopathological response-specific molecular signatures of chemotherapy efficacy."],"pubmed_authors":["Böhm Agnes K AK, Skrip Lisa M LM, Klein Oliver O, Strobl Felix F, Wieland Jonas K JK, Arnold Alexander A, Zhou Yijun Y, Papke Björn B, Sers Christine C, Modest Dominik P DP, Moosburner Simon S, Haber Philipp K PK, Krenzien Felix F, Raschzok Nathanael N, Schöning Wenzel W, Horst David D, Malinka Thomas T, Sack Ingolf I, Pratschke Johann J, Sauer Igor M IM, Hillebrandt Karl H KH"],"additional_accession":[]},"is_claimable":false,"name":"Proteomic Profiling of Colorectal Liver Metastases Reveals Histopathological Response-Specific Molecular Signatures of Chemotherapy Efficacy","description":"Background:  Chemoresistance in treatment of colorectal liver metastases (CRLM) poses a serious challenge in preventing disease relapse, with up to 80% of patients developing drug resistance over the course of treatment. Proteomic signatures of responsive vs. non-responsive metastases can provide insights into functional expression patterns, potentially identifying biomarkers for therapy efficacy.   Methods: A total of 33 CRLM tissue samples from 31 patients were subjected to histopathological and proteomic analysis. The patients were included in the study after undergoing preoperative treatment (n = 28), including platinum-based chemotherapy (n = 19), non-platinum-based chemotherapy (n = 8), as well as targeted therapies (n = 20), or without preoperative therapy (n = 5). Based on Rubbia-Brandt criteria and vital tumor cell percentage, CRLM were categorized to major (MR), partial (PR) and no response (NR) groups. Proteomic analysis was conducted using label-free mass spectrometry (LFQ-MS), followed by clustering according to histological response and distinct treatment regimens.  Results: Proteomic analysis revealed significant differential protein expression of 607 proteins linked to distinct histopathological response types. CRLM responsive to chemotherapy displayed marked enrichment (p ≤ 0.01) in pathways associated with immune infiltration, complement system, ECM matrix organization and apolipoprotein-associated processes, indicative of distinct stromal and immune invasion patterns with multimodal importance of cell adhesion proteins. In contrast, attenuated expression of proteins enriched in pathways of mitochondrial translation initiation, elongation and termination was detectable.   Conclusion: CRLM exhibited distinct proteomic phenotypes based on their histopathological response to preoperative systemic therapy largely independent of chemotherapy regimens. This proteomic profiling establishes a foundation for identifying critical profiles and enhancing our understanding of mechanisms driving tumor response.","dates":{"publication":"2026-04-13","submission":"2025-07-06"},"accession":"PXD065812","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NCBITaxon:12939","NEWT:32046","NEWT:544496","NEWT:59529","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:10245","NEWT:55153","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:351581","NEWT:43186","NEWT:428146","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:1401257","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7719","NEWT:7959","NEWT:2261","NEWT:868565","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:284218","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:5757","NEWT:68415","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:347256","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:145458","NEWT:633149","NEWT:1149786","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:213863","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:2065263","NEWT:177437","NEWT:1772","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:3702","NEWT:1245466","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:586722","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:333760","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NEWT:34613","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:886559","NEWT:3750","NEWT:55521","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:203696","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:5911","NEWT:1313","NEWT:1218097","NEWT:1080348","NCBITaxon:50557","NEWT:39251","NEWT:39491","NEWT:212142","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NCBITaxon:5820","NEWT:1547","NEWT:272634","NEWT:198107","NEWT:9031","NEWT:27292","NEWT:1872122","NEWT:1308","NEWT:7091","NEWT:1034015","NEWT:760568","NEWT:141262","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:97477","NEWT:7111","NEWT:347515","NEWT:172269","NEWT:9534","NEWT:6269","NEWT:5180","NEWT:256737","NEWT:4090","NEWT:4092","NEWT:9541","NEWT:8694","NEWT:4093","NEWT:4096","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:941442","NEWT:536088","NEWT:13076","NEWT:1226408","NEWT:7108","NEWT:40479","NEWT:43989","NEWT:4076","NEWT:142615","NE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