{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:28:20Z","timestamp":1761863300942,"version":"3.37.3"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T00:00:00Z","timestamp":1409616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100737"],"award-info":[{"award-number":["81100737"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"Aims<\/jats:title>Pyruvate kinase M<\/jats:styled-content>2 (PKM<\/jats:styled-content>2) and lactate dehydrogenase 5 (LDH<\/jats:styled-content>5) are two metabolic and oncogenic markers of cancer. In this study, we sought to investigate their expression patterns and prognostic value in tongue squamous cell carcinoma (TSCC<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods and results<\/jats:title>The expression and subcellular localization of PKM<\/jats:styled-content>2 and LDH<\/jats:styled-content>5 in TSCC<\/jats:styled-content> cell lines were determined by W<\/jats:styled-content>estern blot and immunofluorescence. PKM<\/jats:styled-content>2 and LDH<\/jats:styled-content>5 abundance was examined by immunohistochemistry in 63 TSCC<\/jats:styled-content> tumour specimens; their association with multiple clinicopathological parameters and overall patient survival was assessed. The protein levels of PKM<\/jats:styled-content>2 and LDH<\/jats:styled-content>5 were both significantly higher in TSCC<\/jats:styled-content> cells than in an immortalized oral epithelial cell line. Overexpression of PKM<\/jats:styled-content>2 associated significantly with cervical node metastasis (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0373), while elevated LDH<\/jats:styled-content>5 levels correlated significantly with tumour size (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0094), pathological grade (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0052), cervical node metastasis (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0023) and clinical stage (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0024). Patients with tumours showing an increase in either PKM<\/jats:styled-content>2 or LDH<\/jats:styled-content>5 expression displayed significantly reduced overall survival, while patients with tumours overexpressing both proteins showed the worst prognosis with lowest overall survival. Furthermore, PKM<\/jats:styled-content>2 and LDH<\/jats:styled-content>5 were identified as independent prognostic predictors for overall patient survival in TSCC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our data indicate that overexpression of PKM<\/jats:styled-content>2 and LDH<\/jats:styled-content>5 associates with key clinicopathological features and unfavourable prognosis in TSCC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12441","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T04:36:35Z","timestamp":1398400595000},"page":"595-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Overexpression of metabolic markers PKM<\/scp>2 and LDH<\/scp>5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer"],"prefix":"10.1111","volume":"65","author":[{"given":"Chunping","family":"Yuan","sequence":"first","affiliation":[{"name":"Oral Cancer Center Institute of Stomatology Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongwu","family":"Li","sequence":"additional","affiliation":[{"name":"Oral Cancer Center Institute of Stomatology Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Wang","sequence":"additional","affiliation":[{"name":"Oral Cancer Center Institute of Stomatology Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhai","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Nian","family":"Song","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center Columbia University Medical Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianrong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Stomatological Hospital Nanjing Medical University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60728-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2008.12.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.04.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2010.06.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2981"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.021"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2012.04.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0859"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69741"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027309"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2004.08.010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-008-9955-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-013-9601-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014769108"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.054"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.07.018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209597"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914433107"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0026"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.04.023"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23583"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-012-9557-2"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4258"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2007.12.002"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2011.06.003"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.05.9501"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032996"},{"volume-title":"World Health Organization classification of head and neck tumors: pathology and genetics of head and neck tumors","year":"2012","author":"Barnes L","key":"e_1_2_7_31_1"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.4.242"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212780110"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.160"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12062"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0730-x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4145"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000259260"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gms106"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6658"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2629"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.01.001"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.12441","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.12441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:18:03Z","timestamp":1696313883000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.12441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,2]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/his.12441"],"URL":"https:\/\/doi.org\/10.1111\/his.12441","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"type":"print","value":"0309-0167"},{"type":"electronic","value":"1365-2559"}],"subject":[],"published":{"date-parts":[[2014,9,2]]},"assertion":[{"value":"2013-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}