{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:13:59Z","timestamp":1753888439453,"version":"3.41.2"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":119,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070623","31900502","32070157","81900521","81903773"],"award-info":[{"award-number":["32070623","31900502","32070157","81900521","81903773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>The tryptophan residue has a large hydrophobic surface that plays a unique role in the folded protein conformation and functions. Tryptophan modifications are presumably to be readily detected in proteins due to the vulnerability of the indole structure to electrophilic attacks. In this study, we report a systematic identification of sequence variations at tryptophan, termed tryptophan variants, from the proteome of patients with nonsmall cell lung cancer (NSCLC). Using shotgun proteomics and a modified open search algorithm, 25 tryptophan variants on 2481 sites in over 858 proteins were identified. Among these, 6 tryptophan variants are previously identified, 15 are newly annotated, and 4 are still unknown, most of which are involved in the cascade of oxidation in the blood microparticle. Remarkably, Trp313 of glyceraldehyde\u20103\u2010phosphate dehydrogenase (GAPDH) was up\u2010oxidized whereas Trp16 and Trp38 of hemoglobin (HBB) were down\u2010oxidized in NCSLC tissues. The results were further supported by an independent cohort of 103 lung adenocarcinoma samples, reflecting a negative feedback and potential detoxification mechanism against tumor glycolysis and hypoxia. Overall, the study reports a quick approach to explore tryptophan variants at the proteomic scale. Our findings highlight the predominant role of tryptophan oxidation in regulating the redox balance of cancer cells and its potential role as prognostic biomarker for patients with NSCLC.<\/jats:p>","DOI":"10.1155\/2022\/2590198","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T19:35:08Z","timestamp":1651347308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Open Search\u2010Based Proteomics Reveals Widespread Tryptophan Modifications Associated with Hypoxia in Lung Cancer"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-5987","authenticated-orcid":false,"given":"Jinfeng","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinli","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-4735","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqiang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongqiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichao","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-0175","authenticated-orcid":false,"given":"Jing-Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-018-07882-0"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070657"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.037"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1240"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.001"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-11-research0049"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122485"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2005.07.009"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/bmb.2002.494030030035"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312671200"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0305303"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009085200"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(67)90331-2"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001579g"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410853200"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.08.003"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.10.095"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvi095"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.12.017"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00131a030"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.3109\/03630269309043491"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4256"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19949"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1320s40"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2834"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13302"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110137"},{"volume-title":"Mclust Version 4 for R: Normal Mixture Modeling for Model-Based Clustering, Classification, and Density Estimation","year":"2012","author":"Fraley C.","key":"e_1_2_9_29_2"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/comjnl\/41.8.578"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr300073p"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"volume-title":"Molecular Operating Environment (MOE) CCGI","year":"2014","key":"e_1_2_9_36_2"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0SC03805A"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1192"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b02637"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328365aae3"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00316-0"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.080"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.640112"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.11.002"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr700657y"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0000000000000537"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.570275"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9121288"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905042289"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5759"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c080113"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.043"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0491"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104720"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2590198.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2590198.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/2590198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:39:51Z","timestamp":1748907591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/2590198"}},"subtitle":[],"editor":[{"given":"C.","family":"L\u00f3pez-Alarc\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/2590198"],"URL":"https:\/\/doi.org\/10.1155\/2022\/2590198","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"type":"print","value":"1942-0900"},{"type":"electronic","value":"1942-0994"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2021-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2590198"}}