{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:15:19Z","timestamp":1778822119195,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["22ZR1476900"],"award-info":[{"award-number":["22ZR1476900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473892"],"award-info":[{"award-number":["82473892"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003711"],"award-info":[{"award-number":["82003711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma, the third leading cause of cancer\u2010related deaths globally, presents a critical public health burden in China due to its high incidence and mortality. While targeted therapies and immunotherapies have improved survival in advanced HCC, drug resistance remains a major therapeutic challenge. Recent studies suggest that gefitinib, an EGFR inhibitor, overcomes lenvatinib resistance, yet its mechanistic underpinnings are incompletely understood. To investigate gefitinib's metabolic effects in HCC, we conducted untargeted metabolomic profiling using two separate platforms: gas chromatography\u2013mass spectrometry (GC\u2013MS) and liquid chromatography\u2013mass spectrometry (LC\u2013MS) with both hydrophilic interaction liquid chromatography (HILIC) and reversed\u2010phase modes. Raw data were processed by Mass Hunter, normalized with internal standards, and analyzed via SIMCA for pattern recognition. Principal component analysis (PCA) of quality control samples and experimental groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096 each) confirmed system stability and clear inter\u2010group separation. Orthogonal projections to latent structures discriminant analysis models were validated by 200 permutation tests. Analysis identified 42 metabolites with VIP &gt;\u20091, of which 25 showed significant alterations (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) post\u2010gefitinib treatment. KEGG\/RaMP\u2010DB enrichment revealed perturbations in four key pathways: arginine\u2010proline metabolism, nitrogen metabolism, branched\u2010chain amino acid biosynthesis, and taurine metabolism. These results delineate gefitinib\u2010induced metabolic reprogramming in HCC cells, providing a foundation for targeting metabolic vulnerabilities to overcome therapy resistance.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70470","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:48:57Z","timestamp":1777506537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GC\/MS and LC\/MS Metabolomic Analysis of Gefitinib in Liver Cancer"],"prefix":"10.1002","volume":"40","author":[{"given":"Dan","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy Naval Medical University  Shanghai China"},{"name":"Department of Pharmacy Third Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Medical College Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shitao","family":"Chen","sequence":"additional","affiliation":[{"name":"Basic Medical College Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Medical College Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lv","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine First Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5852-2640","authenticated-orcid":false,"given":"DongYao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4403-4598","authenticated-orcid":false,"given":"Leilei","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Third Affiliated Hospital of Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-4311","authenticated-orcid":false,"given":"Diya","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Pharmacy Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.71"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.025"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.023"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69600"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953115"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113873109"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38360-5"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2803"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010019\u20100040\u20105"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02075-w"}],"container-title":["Biomedical 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