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Lilla"],"technology_type":["Mass Spectrometry","Data-independent acquisition"],"disease":["Pancreatic Ductal Adenocarcinoma"],"software":[""],"submitter_keywords":["Biomarker","Pancreatic ductal adenocarcinoma","Serum","pancreatic intraepithelial neoplasia","Pancreatic ductal adenocarcinoma; pancreatic intraepithelial neoplasia","Autophagy","Early detection"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD065698"],"tissue":["Blood Serum"],"sample_protocol":["Aliquots of one microliter of mouse serum sample were reduced, alkylated, digested on MagRes hydroxyl beads and desalted (Resyn Bioscience) by mean of an AssayMap Bravo equipped with a the 96LT or AssayMap head (Agilent). Serum digests were analysed using a reverse-phase C18 column on an EASY-nLC II 1200, coupled to a Q-Exactive HF mass spectrometer. Elution of peptides was carried out at 300 nl/minute over a 90 minutes gradient. Samples were loaded into a 50 cm fused silica emitter (CooAnn) packed in-house with ReproSil-Pur C18-AQ, 1.9 µm resin (Dr Maisch GmbH). The packed emitter was held at 50°C using a column oven (Sonation) integrated into the nano-electrospray ion source (Thermo Scientific). An Active Background Ion Reduction Device (ABIRD) was used to reduce ambient contaminant signal level. The spray voltage was set to 2.1 kV and ion transfer tube temperature to 250°C. Xcalibur software (Thermo Scientific) was used for data acquisition which was carried out in positive ion mode using data independent acquisition (DIA). A full scan over a mass range of 340–1050 m/z was acquired at 60,000 resolution, at 200 m/z, with a target value of 3,000,000 ions for a maximum injection time of 54 ms. Higher energy collisional dissociation fragmentation spectra were recorded at 30000 resolution, at 200 m/z. All precursors were fragmented using 28 consecutive windows with 25 Da width, allowing for a 0.5 m/z overlap, covering a mass range from 350-1023 m/z. All ions were fragmented using a normalised collision energy of 28, for a maximum injection time of 54 ms, or a target value of 30,000 ions."],"repository":["Pride"],"modification":[""],"quantification_method":[""],"data_protocol":["Raw data were processed using Spectronaut version 18.2 (Mouse) or 19.0 (Human) (Biognosys) in directDIA using the UniProt databases (Mus musculus (25,198 entries) or Homo sapiens (42,438 entries)). Minimum peptide length was set to seven amino acids and specificity for trypsin/P cleavage was required, allowing up to two missed cleavage sites. Methionine oxidation and N-terminal acetylation were specified as variable modifications, whereas carbamidomethylation of cysteine was set as fixed modification. Minor peptide grouping was set to ‘Modified Sequence’, and  Major and Minor Group Quantity were set to ‘Sum peptide quantity’ and ‘Median precursor quantity’ respectively. Single hit proteins were excluded from the dataset and all other Spectronaut parameters were left to their default options."],"omics_type":["Proteomics"],"labhead":["Kevin Ryan"],"instrument_platform":[""],"labhead_affiliation":["CRUK -CRUK Scotland Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"publication":["41709591 Mearns H, Long JS, Lilla S, Hodge K, Ladds MJGW, Nixon C, Fernández-Palanca P, Zanivan S, Acedo P, Pereira SP, Ryan KM. Identification of serum protein biomarkers for pre-cancerous lesions associated with pancreatic ductal adenocarcinoma. Mol Oncol. 2026 20(6):1473-1493 10.1002/1878-0261.70213"],"submitter_mail":["s.lilla@beatson.gla.ac.uk"],"submitter_affiliation":["Proteomics"],"submitter_country":["United Kingdom"],"pubmed_abstract":["Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis as early-stage asymptomaticity leads to late-stage diagnoses. Strategies to detect PDAC earlier or identify high-risk individuals are therefore paramount. Here, we report results from genetically engineered mice and PDAC patients that identify serum proteins associated with pancreatic intraepithelial neoplasms (PanINs), the most common PDAC precursor, and early-stage PDAC. Initially, we screened previously described PanIN-abundant mice, harbouring pancreatic and duodenal homeobox 1 (Pdx1)-Cre, Lox-STOP-Lox-Kras<sup>G12D/+</sup> and floxed alleles of essential autophagy genes autophagy-related 7 (Atg7) or autophagy-related 5 (Atg5). Sera from these mice were assessed by proteomics and hits were compared to those in Lox-STOP-Lox-Kras<sup>G12D/+</sup> Lox-STOP-Lox-Trp53<sup>R172H/+</sup> Pdx1-Cre (KPC) mice, which closely recapitulate human disease, and early-stage (I-II) PDAC patients. Levels of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were significantly elevated in all three screens, with complement C5, complement factors B and H (CFB/CFH), and monocyte differentiation antigen CD14 increased in KPC mice and PDAC patients; and all were significantly increased co-ordinately in PDAC according to disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with confidence, and when combined with additional screening, could help increase survival from this dismal disease."],"pubmed_title":["Identification of serum protein biomarkers for pre-cancerous lesions associated with pancreatic ductal adenocarcinoma."],"pubmed_authors":["Mearns Hannah H, Long Jaclyn S JS, Lilla Sergio S, Hodge Kelly K, Ladds Marcus J G W MJGW, Nixon Colin C, Fernández-Palanca Paula P, Zanivan Sara S, Acedo Pilar P, Pereira Stephen P SP, Ryan Kevin M KM"],"additional_accession":[]},"is_claimable":false,"name":"Identification of serum protein biomarkers for pre-cancerous lesions associated with Pancreatic Ductal Adenocarcinoma (Part2 : KPC-Mice)","description":"Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis as early-stage asymptomaticity leads to late-stage diagnoses. Strategies to detect PDAC earlier or identify predisposed individuals are therefore paramount. Here we report results from genetically engineered mice (GEMMs) and PDAC patients that identify serum proteins associated with pancreatic intraepithelial neoplasms (PanINs) (the most common PDAC precursor) and early-stage PDAC. Initially we screened previously described PanIN-abundant GEMMs, harbouring Pdx1-Cre, Lox-STOP-Lox-KrasG12D/+ and floxed alleles of essential autophagy genes Atg7-/- or Atg5-/-. Serum from these mice was assessed by proteomics and hits compared to those identified in KrasG12D/+ Trp53R172H/+ Pdx1-Cre (KPC) mice (which closely recapitulate human disease) and early-stage (I-II) PDAC patients. Inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) was elevated in all three screens, with complement C5, complement factors B and H, and CD14 increased in KPC mice and PDAC patients; all significantly increase co-ordinately in PDAC, with each elevating with disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with confidence, and when combined with additional screening could help increase survival from this significant disease.","dates":{"publication":"2026-06-15","submission":"2025-07-02"},"accession":"PXD065698","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:109760","NEWT:29031","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:472","NEWT:1071661","NEWT:470","NEWT:5911","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:9031","NEWT:27292","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:1006581","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:8655","NEWT:5147","NEWT:28104","NEWT:407821","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:6063","NEWT:1328388","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:80863","NEWT:90675","NEWT:52638","NEWT:57075","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","NEWT:90690","NEWT:1436183","NEWT:4232","NEWT:416348","NEWT:11298","NEWT:196627","NEWT:200308","NEWT:200302","NEWT:870435","NEWT:9913","NEWT:9915","NEWT:105841","NEWT:2666255","NEWT:999810","NCBITaxon:5693","NEWT:28995","NEWT:1392998","NEWT:380394","NEWT:226900","NEWT:1266738","NEWT:231490","NEWT:244704","NEWT:7725","NEWT:430615","NEWT:563041","NEWT:72664","NEWT:326423","NEWT:452467","NEWT:198822","NEWT:36111","NEWT:326424","NEWT:1678078","NEWT:749906","NEWT:418985","NEWT:749907","NEWT:150847","NEWT:431947","NEWT:69014","NEWT:142809","NEWT:302409","NEWT:130821","NEWT:27606","NEWT:1519788","NEWT:59202","NEWT:9975","NEWT:8643","NEWT:1159899","NEWT:502780","NEWT:860688","NEWT:13443","NEWT:8644","NEWT:5141","NEWT:46360","NCBITaxon:3044782","NEWT:202914","NEWT:160235","NEWT:502779","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