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Liao"],"technology_type":["Mass Spectrometry","Shotgun proteomics"],"software":["Not available"],"submitter_keywords":["Lysine 2-hydroxyisobutyrylation","Cancer metastasis","Proteomics"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD038252"],"sample_protocol":["Biospecimens were collected from newly diagnosed patients who underwent surgical resection (Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China). All sample collection procedures complied with routine clinical practice. Protein sample preparation and liquid chromatography–tandem mass spectrometry (LC–MS/MS) using the Tandem Mass Tag (TMT) were performed at PTM Biolab Co. Ltd. (Hangzhou, Zhejiang, China). Fresh tissue samples were ground into a powder under liquid nitrogen, and lysis buffer (8 mol/L urea and 1% protease inhibitor cocktail) was added to lyse cells. This step was followed by three rounds of sonication on ice using a high-intensity ultrasonic processor (for cell sample, it was immediately sonicated three times on ice using a high-intensity ultrasonic processor in lysis buffer). For PTM assays, inhibitors were added to the lysis buffer, e.g., 3 μM trichostatin A (TSA) and 50 mM nicotinamide (NAM) to maintain acetylation and 1% phosphatase inhibitor to maintain phosphorylation. After centrifugation at 12,000 × g and 4°C for 10 min, the supernatant was collected, and the protein concentration was determined. For digestion, proteins in the solution were reduced by incubation with 5 mM dithiothreitol for 30 min at 56°C and alkylated with 11 mM iodoacetamide for 15 min at room temperature in the dark. The protein sample was then diluted with 100 mM triethylammonium bicarbonate (TEAB) to achieve a urea concentration of less than 2 M. Finally, trypsin was added at a 1:50 trypsin:protein mass ratio for initial digestion overnight and a 1:100 trypsin:protein mass ratio for a second 4-h digestion."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Bioinformatics Methods Annotation Methods GO Annotation,Domain Annotation,KEGG Pathway Annotation,Subcellular Localization Motif Analysis Soft MoMo (motif-x algorithm) was used to analysis the model of sequences constituted with amino acids in specific positions of modify-21-mers (10 amino acids upstream and downstream of the site， but phosphorylation with modify-13-mers that 6 amino acids upstream and downstream of the site) in all protein sequences. And all the database protein sequences were used as background database parameter. Minimum number of occurrences was set to 20. Emulate original motif-x was ticked, and other parameters with default."],"omics_type":["Proteomics"],"labhead":["Bin Li"],"instrument_platform":[""],"labhead_affiliation":["The Fifth Affiliated Hospital of Guangzhou Medical University"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"publication":["42327710 Li J, Li S, Yu X, Mu Q, Luo M, Wang Y, Liu Z, Gu C, Chen J, He W, Yang T, He Y, Pei X, Lin M, Li Z, Liu J, Zhao B, Zhang F, Liu J, Li B, Xu W. 2-Hydroxyisobutyrylation and Phosphorylation Crosstalk Guides Metastasis Prediction and Immunotherapy in Esophageal Squamous Cell Carcinoma. MedComm (2020). 2026 7(7):e70815 10.1002/mco2.70815"],"submitter_mail":["liaolo20@stu2017.jnu.edu.cn"],"submitter_affiliation":["The Fifth Affiliated Hospital of Guangzhou Medical University"],"submitter_country":["China"],"pubmed_abstract":["Posttranslational modification (PTM) is pivotal in cancer progression. However, the mechanisms, biological function, and clinical significance underlying PTM crosstalk are unclear. Here, we performed systematic analyses of 2-hydroxyisobutyrylation (Khib), phosphoproteomic, proteomic, and transcriptomic profiles from 60 esophageal squamous cell carcinoma (ESCC) samples, comprising matched normal, primary tumor, and metastatic lymph node tissues. The integrative analysis identified 4499 proteins co-modified by Khib and phosphorylation on distinct residues. Interestingly, while the two PTMs target distinct motifs across proteins, they engage common motifs within individual proteins. Functionally, Khib and phosphorylation show prevalent positive crosstalk linked to metastatic progression. Mechanistically, Khib mediates this intra-protein crosstalk by recruiting kinases and potentiating phosphorylation events. Machine learning-based artificial intelligence (AI) analysis of secreted proteins with PTM crosstalk revealed an independent and highly effective plasma signature predicting lymph node metastasis. Moreover, molecular subtyping stratified ESCC into three groups, with immunotherapy-resistant Subtype 3 associated with the worst survival. While combined treatment of integrin inhibitor cilengitide and immunotherapy exhibited targeted efficacy. By deciphering the mechanistic basis of Khib-phosphorylation crosstalk, identifying a novel plasma biomarker for lymph node metastasis, and providing a therapeutic strategy to sensitize tumors to immunotherapy, this work collectively advances the precision diagnosis and treatment of ESCC."],"pubmed_title":["2-Hydroxyisobutyrylation and Phosphorylation Crosstalk Guides Metastasis Prediction and Immunotherapy in Esophageal Squamous Cell Carcinoma."],"pubmed_authors":["Li Junyi J, Li Shujun S, Yu Xiaomei X, Mu Qier Q, Luo Maowen M, Wang Yuzhen Y, Liu Zhichao Z, Gu Chengwei C, Chen Jiaxi J, He Wangcheng W, Yang Tong T, He Yan Y, Pei Xiaoya X, Lin Mao M, Li Zhigang Z, Liu Jun J, Zhao Baosheng B, Zhang Fan F, Liu Jinbao J, Li Bin B, Xu Wenwen W"],"additional_accession":[]},"is_claimable":false,"name":"Quantitative Khib proteomic analyses of 20 cases of primary ESCC tumor tissue (T), matched normal tissue (N) and lymph node metastatic tissue (LN)","description":"To obtain the global landscape of Khib in ESCC metastasis, 20 cases of primary ESCC tumor tissue (T), matched normal tissue (N) and lymph node metastatic tissue (LN) were subjected to quantitative Khib proteomic analyses.","dates":{"publication":"2026-06-29","submission":"2022-11-22"},"accession":"PXD038252","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NCBITaxon:12939","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","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","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:1214915","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:1912919","NEWT:5757","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:1367269","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:1235816","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:270643","NEWT:2065263","NEWT:177437","NEWT:1772","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:459758","NEWT:3702","NEWT:1245466","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:586722","NEWT:2850","NEWT:118691","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:9483","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: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","NE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