{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:03:04Z","timestamp":1775149384016,"version":"3.50.1"},"reference-count":39,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>&lt;p&gt;Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Methods: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis\/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites. Results: ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017). Conclusion: 2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000548128","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T16:01:30Z","timestamp":1756396890000},"page":"72-86","source":"Crossref","is-referenced-by-count":0,"title":["2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma"],"prefix":"10.1159","volume":"93","author":[{"given":"Hiroki","family":"Takase","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8181-6241","authenticated-orcid":false,"given":"Hideki","family":"Makinoshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyoshi","family":"Soga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24915"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2023.07.003"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00224-3"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-6264"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkz055"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01297-0"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02903"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1939"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0109"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92948-9"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8105735"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16030504"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20579"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2007.06.007"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-009-0178-y"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25881"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1021\/pr200800w"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1002\/hed.10125"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00526"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21670"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14411"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1021\/ac990976y"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1021\/pr034020m"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601876200"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1021\/ac020064n"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1021\/ac900675k"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae253"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14432"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0016-5"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/104024"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3831"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.621944"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-005-8469-y"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.05.002"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4101-07.2007"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.10.002"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2013.01.004"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00311-7"}],"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000548128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:02:36Z","timestamp":1775145756000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000548128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4,2]]}},"URL":"https:\/\/doi.org\/10.1159\/000548128","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.29987392","asserted-by":"subject"}]},"ISSN":["1015-2008","14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