{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:32:35Z","timestamp":1790519555936,"version":"4.1.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant 81900168"],"award-info":[{"award-number":["Grant 81900168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["Grant 2020M681181"],"award-info":[{"award-number":["Grant 2020M681181"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["Grant 2022M710766"],"award-info":[{"award-number":["Grant 2022M710766"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant and fatal liver tumor with increasing incidence worldwide. Lactate metabolism has been recently reported as a crucial contributor to tumor progression and immune regulation in the tumor microenvironment. However, it remains poorly identified about the biological functions of lactate metabolism in iCCA, which hinders the development of prognostic tools and therapeutic interventions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The univariate Cox regression analysis and Boruta algorithm were utilized to identify key lactate metabolism-related genes (LMRGs), and a prognostic signature was constructed based on LMRG scores. Genomic variations and immune cell infiltration were evaluated in the high and low LMRG score groups. Finally, the biological functions of key LMRGs were verified with in vitro and in vivo experiments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Patients in the high LMRG score group exhibit a poor prognosis compared to those in the low LMRG score group, with a high frequency of <jats:italic>TP53<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> mutations. Moreover, the infiltration and function of NK cells were compromised in the high LMRG score group, consistent with the results from two independent single-cell RNA sequencing datasets and immunohistochemistry of tissue microarrays. Experimental data revealed that lactate dehydrogenase A (<jats:italic>LDHA<\/jats:italic>) knockdown inhibited proliferation and migration in iCCA cell lines and tumor growth in immunocompetent mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study revealed the biological roles of <jats:italic>LDHA<\/jats:italic> in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-024-05723-4","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T17:01:47Z","timestamp":1713286907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Identification and validation of a lactate metabolism-related six-gene prognostic signature in intrahepatic cholangiocarcinoma"],"prefix":"10.1007","volume":"150","author":[{"given":"Chen","family":"Sang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youpei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"5723_CR1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.ccell.2021.05.010","volume":"39","author":"S Affo","year":"2021","unstructured":"Affo S, Nair A, Brundu F, Ravichandra A, Bhattacharjee S, Matsuda M, Chin L, Filliol A, Wen W, Song X, Decker A, Worley J, Caviglia JM, Yu L, Yin D, Saito Y, Savage T, Wells RG, Mack M, Zender L, Arpaia N, Remotti HE, Rabadan R, Sims P, Leblond AL, Weber A, Riener MO, Stockwell BR, Gaublomme J, Llovet JM, Kalluri R, Michalopoulos GK, Seki E, Sia D, Chen X, Califano A, Schwabe RF (2021) Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39:883. https:\/\/doi.org\/10.1016\/j.ccell.2021.05.010","journal-title":"Cancer Cell"},{"issue":"1282\u201393","key":"5723_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.018","volume":"25","author":"A Angelin","year":"2017","unstructured":"Angelin A, Gil-de-Gomez L, Dahiya S, Jiao J, Guo L, Levine MH, Wang Z, Quinn WJ 3rd, Kopinski PK, Wang L, Akimova T, Liu Y, Bhatti TR, Han R, Laskin BL, Baur JA, Blair IA, Wallace DC, Hancock WW, Beier UH (2017) \u2019Foxp3 reprograms T cell metabolism to function in low-glucose high-lactate environments. Cell Metab 25(1282\u201393):e7. https:\/\/doi.org\/10.1016\/j.cmet.2016.12.018","journal-title":"Cell Metab"},{"key":"5723_CR3","doi-asserted-by":"publisher","first-page":"e173","DOI":"10.1016\/S1470-2045(14)71116-7","volume":"16","author":"VP Balachandran","year":"2015","unstructured":"Balachandran VP, Gonen M, Smith JJ, DeMatteo RP (2015) Nomograms in oncology: more than meets the eye. Lancet Oncol 16:e173\u2013e180. https:\/\/doi.org\/10.1016\/S1470-2045(14)71116-7","journal-title":"Lancet Oncol"},{"key":"5723_CR4","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","volume":"24","author":"A Brand","year":"2016","unstructured":"Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, Kastenberger M, Bogdan C, Schleicher U, Mackensen A, Ullrich E, Fichtner-Feigl S, Kesselring R, Mack M, Ritter U, Schmid M, Blank C, Dettmer K, Oefner PJ, Hoffmann P, Walenta S, Geissler EK, Pouyssegur J, Villunger A, Steven A, Seliger B, Schreml S, Haferkamp S, Kohl E, Karrer S, Berneburg M, Herr W, Mueller-Klieser W, Renner K, Kreutz M (2016) LDHA-Associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab 24:657\u2013671. https:\/\/doi.org\/10.1016\/j.cmet.2016.08.011","journal-title":"Cell Metab"},{"key":"5723_CR5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","volume":"7","author":"PJ Brindley","year":"2021","unstructured":"Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE, Teh BT, Wongkham S, Gores GJ (2021) Cholangiocarcinoma. Nat Rev Dis Primers 7:65. https:\/\/doi.org\/10.1038\/s41572-021-00300-2","journal-title":"Nat Rev Dis Primers"},{"key":"5723_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1474","volume":"12","author":"M Certo","year":"2020","unstructured":"Certo M, Marone G, de Paulis A, Mauro C, Pucino V (2020) Lactate: fueling the fire starter. Wiley Interdiscip Rev Syst Biol Med 12:e1474. https:\/\/doi.org\/10.1002\/wsbm.1474","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"5723_CR7","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41577-020-0406-2","volume":"21","author":"M Certo","year":"2021","unstructured":"Certo M, Tsai CH, Pucino V, Ho PC, Mauro C (2021) Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat Rev Immunol 21:151\u2013161. https:\/\/doi.org\/10.1038\/s41577-020-0406-2","journal-title":"Nat Rev Immunol"},{"key":"5723_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002305","author":"H Deng","year":"2021","unstructured":"Deng H, Kan A, Lyu N, He M, Huang X, Qiao S, Li S, Lu W, Xie Q, Chen H, Lai J, Chen Q, Jiang X, Liu S, Zhang Z, Zhao M (2021) Tumor-derived lactate inhibit the efficacy of lenvatinib through regulating PD-L1 expression on neutrophil in hepatocellular carcinoma. J Immunother Cancer. https:\/\/doi.org\/10.1136\/jitc-2020-002305","journal-title":"J Immunother Cancer"},{"key":"5723_CR9","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/hep.32624","volume":"77","author":"M Deng","year":"2023","unstructured":"Deng M, Ran P, Chen L, Wang Y, Yu Z, Cai K, Feng J, Qin Z, Yin Y, Tan S, Liu Y, Xu C, Shi G, Ji Y, Zhao JY, Zhou J, Fan J, Hou Y, Ding C (2023) Proteogenomic characterization of cholangiocarcinoma. Hepatology 77:411\u2013429. https:\/\/doi.org\/10.1002\/hep.32624","journal-title":"Hepatology"},{"key":"5723_CR10","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1136\/jcp.48.9.876","volume":"48","author":"S Detre","year":"1995","unstructured":"Detre S, Saclani Jotti G, Dowsett M (1995) A \u201cquickscore\u201d method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48:876\u2013878. https:\/\/doi.org\/10.1136\/jcp.48.9.876","journal-title":"J Clin Pathol"},{"key":"5723_CR11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jhep.2018.02.029","volume":"69","author":"LQ Dong","year":"2018","unstructured":"Dong LQ, Shi Y, Ma LJ, Yang LX, Wang XY, Zhang S, Wang ZC, Duan M, Zhang Z, Liu LZ, Zheng BH, Ding ZB, Ke AW, Gao DM, Yuan K, Zhou J, Fan J, Xi R, Gao Q (2018) Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma. J Hepatol 69:89\u201398. https:\/\/doi.org\/10.1016\/j.jhep.2018.02.029","journal-title":"J Hepatol"},{"key":"5723_CR12","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2019.12.014","volume":"72","author":"LQ Dong","year":"2020","unstructured":"Dong LQ, Peng LH, Ma LJ, Liu DB, Zhang S, Luo SZ, Rao JH, Zhu HW, Yang SX, Xi SJ, Chen M, Xie FF, Li FQ, Li WH, Ye C, Lin LY, Wang YJ, Wang XY, Gao DM, Zhou H, Yang HM, Wang J, Zhu SD, Wang XD, Cao Y, Zhou J, Fan J, Wu K, Gao Q (2020) Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma. J Hepatol 72:896\u2013908. https:\/\/doi.org\/10.1016\/j.jhep.2019.12.014","journal-title":"J Hepatol"},{"issue":"70\u201387","key":"5723_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.12.006","volume":"40","author":"L Dong","year":"2022","unstructured":"Dong L, Lu D, Chen R, Lin Y, Zhu H, Zhang Z, Cai S, Cui P, Song G, Rao D, Yi X, Wu Y, Song N, Liu F, Zou Y, Zhang S, Zhang X, Wang X, Qiu S, Zhou J, Wang S, Zhang X, Shi Y, Figeys D, Ding L, Wang P, Zhang B, Rodriguez H, Gao Q, Gao D, Zhou H, Fan J (2022) Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma. Cancer Cell 40(70\u201387):e15. https:\/\/doi.org\/10.1016\/j.ccell.2021.12.006","journal-title":"Cancer Cell"},{"key":"5723_CR14","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1245\/s10434-010-0985-4","volume":"17","author":"SB Edge","year":"2010","unstructured":"Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471\u20131474. https:\/\/doi.org\/10.1245\/s10434-010-0985-4","journal-title":"Ann Surg Oncol"},{"issue":"358\u201371","key":"5723_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.019","volume":"171","author":"B Faubert","year":"2017","unstructured":"Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ (2017) Lactate metabolism in human lung tumors. Cell 171(358\u201371):e9. https:\/\/doi.org\/10.1016\/j.cell.2017.09.019","journal-title":"Cell"},{"issue":"217\u201332","key":"5723_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.013","volume":"53","author":"DR Glass","year":"2020","unstructured":"Glass DR, Tsai AG, Oliveria JP, Hartmann FJ, Kimmey SC, Calderon AA, Borges L, Glass MC, Wagar LE, Davis MM, Bendall SC (2020) An Integrated multi-omic single-cell atlas of human B cell identity. Immunity 53(217\u201332):e5. https:\/\/doi.org\/10.1016\/j.immuni.2020.06.013","journal-title":"Immunity"},{"key":"5723_CR17","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202115343","volume":"14","author":"J Guyon","year":"2022","unstructured":"Guyon J, Fernandez-Moncada I, Larrieu CM, Bouchez CL, Pagano Zottola AC, Galvis J, Chouleur T, Burban A, Joseph K, Ravi VM, Espedal H, Rosland GV, Daher B, Barre A, Dartigues B, Karkar S, Rudewicz J, Romero-Garmendia I, Klink B, Grutzmann K, Derieppe MA, Molinie T, Obad N, Leon C, Seano G, Miletic H, Heiland DH, Marsicano G, Nikolski M, Bjerkvig R, Bikfalvi A, Daubon T (2022) Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis. EMBO Mol Med 14:e15343. https:\/\/doi.org\/10.15252\/emmm.202115343","journal-title":"EMBO Mol Med"},{"key":"5723_CR18","doi-asserted-by":"publisher","first-page":"211","DOI":"10.21037\/hbsn.2019.10.11","volume":"9","author":"E Herraez","year":"2020","unstructured":"Herraez E, Romero MR, Macias RIR, Monte MJ, Marin JJG (2020) \u201cClinical relevance of the relationship between changes in gut microbiota and bile acid metabolism in patients with intrahepatic cholangiocarcinoma\u201d, Hepatobiliary Surg. Nutr 9:211\u2013214. https:\/\/doi.org\/10.21037\/hbsn.2019.10.11","journal-title":"Nutr"},{"key":"5723_CR19","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s13045-020-01005-x","volume":"13","author":"M Hong","year":"2020","unstructured":"Hong M, Tao S, Zhang L, Diao LT, Huang X, Huang S, Xie SJ, Xiao ZD, Zhang H (2020) RNA sequencing: new technologies and applications in cancer research. J Hematol Oncol 13:166. https:\/\/doi.org\/10.1186\/s13045-020-01005-x","journal-title":"J Hematol Oncol"},{"key":"5723_CR20","doi-asserted-by":"publisher","first-page":"22449","DOI":"10.1038\/srep22449","volume":"6","author":"L Huang","year":"2016","unstructured":"Huang L, Yu Z, Zhang Z, Ma W, Song S, Huang G (2016) Interaction with pyruvate kinase M2 destabilizes tristetraprolin by proteasome degradation and regulates cell proliferation in breast cancer. Sci Rep 6:22449. https:\/\/doi.org\/10.1038\/srep22449","journal-title":"Sci Rep"},{"key":"5723_CR21","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.4049\/jimmunol.1202702","volume":"191","author":"Z Husain","year":"2013","unstructured":"Husain Z, Huang Y, Seth P, Sukhatme VP (2013) Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol 191:1486\u20131495. https:\/\/doi.org\/10.4049\/jimmunol.1202702","journal-title":"J Immunol"},{"key":"5723_CR22","doi-asserted-by":"publisher","first-page":"3868","DOI":"10.7150\/thno.53347","volume":"11","author":"Y Jiang","year":"2021","unstructured":"Jiang Y, Li F, Gao B, Ma M, Chen M, Wu Y, Zhang W, Sun Y, Liu S, Shen H (2021) KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma. Theranostics 11:3868\u20133881. https:\/\/doi.org\/10.7150\/thno.53347","journal-title":"Theranostics"},{"key":"5723_CR23","doi-asserted-by":"publisher","first-page":"W212","DOI":"10.1093\/nar\/gkz446","volume":"47","author":"AB Keenan","year":"2019","unstructured":"Keenan AB, Torre D, Lachmann A, Leong AK, Wojciechowicz ML, Utti V, Jagodnik KM, Kropiwnicki E, Wang Z, Ma\u2019ayan A (2019) ChEA3: transcription factor enrichment analysis by orthogonal omics integration. Nucleic Acids Res 47:W212\u2013W224. https:\/\/doi.org\/10.1093\/nar\/gkz446","journal-title":"Nucleic Acids Res"},{"key":"5723_CR24","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jhep.2019.10.009","volume":"72","author":"RK Kelley","year":"2020","unstructured":"Kelley RK, Bridgewater J, Gores GJ, Zhu AX (2020) Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol 72:353\u2013363. https:\/\/doi.org\/10.1016\/j.jhep.2019.10.009","journal-title":"J Hepatol"},{"key":"5723_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v036.i11","volume":"36","author":"MB Kursa","year":"2010","unstructured":"Kursa MB, Rudnicki WR (2010) Feature selection with the boruta package. J Stat Softw 36:1\u201313. https:\/\/doi.org\/10.18637\/jss.v036.i11","journal-title":"J Stat Softw"},{"key":"5723_CR26","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1073\/pnas.0914433107","volume":"107","author":"A Le","year":"2010","unstructured":"Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV (2010) Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A 107:2037\u20132042. https:\/\/doi.org\/10.1073\/pnas.0914433107","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5723_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.801959","volume":"9","author":"Y Li","year":"2021","unstructured":"Li Y, Mo H, Wu S, Liu X, Tu K (2021) A novel lactate metabolism-related gene signature for predicting clinical outcome and tumor microenvironment in hepatocellular carcinoma. Front Cell Dev Biol 9:801959. https:\/\/doi.org\/10.3389\/fcell.2021.801959","journal-title":"Front Cell Dev Biol"},{"key":"5723_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.998140","volume":"13","author":"J Li","year":"2022","unstructured":"Li J, Qiao H, Wu F, Sun S, Feng C, Li C, Yan W, Lv W, Wu H, Liu M, Chen X, Liu X, Wang W, Cai Y, Zhang Y, Zhou Z, Zhang Y, Zhang S (2022) A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses. Front Immunol 13:998140. https:\/\/doi.org\/10.3389\/fimmu.2022.998140","journal-title":"Front Immunol"},{"key":"5723_CR29","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/cr.2016.159","volume":"27","author":"J Liang","year":"2017","unstructured":"Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P, Li D, Li W, Yang W (2017) Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Cell Res 27:329\u2013351. https:\/\/doi.org\/10.1038\/cr.2016.159","journal-title":"Cell Res"},{"key":"5723_CR30","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004892","author":"J Lin","year":"2022","unstructured":"Lin J, Dai Y, Sang C, Song G, Xiang B, Zhang M, Dong L, Xia X, Ma J, Shen X, Ji S, Zhang S, Wang M, Fang H, Zhang X, Wang X, Zhang B, Zhou J, Fan J, Zhou H, Gao D, Gao Q (2022a) Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities. J Immunother Cancer. https:\/\/doi.org\/10.1136\/jitc-2022-004892","journal-title":"J Immunother Cancer"},{"key":"5723_CR31","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1158\/2159-8290.CD-21-1640","volume":"12","author":"Y Lin","year":"2022","unstructured":"Lin Y, Peng L, Dong L, Liu D, Ma J, Lin J, Chen X, Lin P, Song G, Zhang M, Liu Y, Rao J, Wei C, Lu Y, Zhang S, Ding G, Peng Z, Lu H, Wang X, Zhou J, Fan J, Wu K, Gao Q (2022b) Geospatial immune heterogeneity reflects the diverse tumor-immune interactions in intrahepatic cholangiocarcinoma. Cancer Discov 12:2350\u20132371. https:\/\/doi.org\/10.1158\/2159-8290.CD-21-1640","journal-title":"Cancer Discov"},{"key":"5723_CR32","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"5723_CR33","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/j.jhep.2021.06.028","volume":"75","author":"L Ma","year":"2021","unstructured":"Ma L, Wang L, Khatib SA, Chang CW, Heinrich S, Dominguez DA, Forgues M, Candia J, Hernandez MO, Kelly M, Zhao Y, Tran B, Hernandez JM, Davis JL, Kleiner DE, Wood BJ, Greten TF, Wang XW (2021) Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Hepatol 75:1397\u20131408. https:\/\/doi.org\/10.1016\/j.jhep.2021.06.028","journal-title":"J Hepatol"},{"key":"5723_CR34","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.cmet.2014.05.004","volume":"20","author":"AN Macintyre","year":"2014","unstructured":"Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC (2014) The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 20:61\u201372. https:\/\/doi.org\/10.1016\/j.cmet.2014.05.004","journal-title":"Cell Metab"},{"key":"5723_CR35","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-020-01976-x","author":"PJ Martinez","year":"2020","unstructured":"Martinez PJ, Agudiez M, Molero D, Martin-Lorenzo M, Baldan-Martin M, Santiago-Hernandez A, Garcia-Segura JM, Madruga F, Cabrera M, Calvo E, Ruiz-Hurtado G, Barderas MG, Vivanco F, Ruilope LM, Alvarez-Llamas G (2020) Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations. J Mol Med (berl). https:\/\/doi.org\/10.1007\/s00109-020-01976-x","journal-title":"J Mol Med (berl)"},{"key":"5723_CR36","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1158\/1078-0432.CCR-12-2638","volume":"19","author":"ML McCleland","year":"2013","unstructured":"McCleland ML, Adler AS, Deming L, Cosino E, Lee L, Blackwood EM, Solon M, Tao J, Li L, Shames D, Jackson E, Forrest WF, Firestein R (2013) Lactate dehydrogenase B is required for the growth of KRAS-dependent lung adenocarcinomas. Clin Cancer Res 19:773\u2013784. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-2638","journal-title":"Clin Cancer Res"},{"key":"5723_CR37","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1126\/science.aaf6284","volume":"354","author":"M Peng","year":"2016","unstructured":"Peng M, Yin N, Chhangawala S, Xu K, Leslie CS, Li MO (2016) Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science 354:481\u2013484. https:\/\/doi.org\/10.1126\/science.aaf6284","journal-title":"Science"},{"issue":"1055\u201374","key":"5723_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.004","volume":"30","author":"V Pucino","year":"2019","unstructured":"Pucino V, Certo M, Bulusu V, Cucchi D, Goldmann K, Pontarini E, Haas R, Smith J, Headland SE, Blighe K, Ruscica M, Humby F, Lewis MJ, Kamphorst JJ, Bombardieri M, Pitzalis C, Mauro C (2019) Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4(+) T cell metabolic rewiring. Cell Metab 30(1055\u201374):e8. https:\/\/doi.org\/10.1016\/j.cmet.2019.10.004","journal-title":"Cell Metab"},{"key":"5723_CR39","doi-asserted-by":"publisher","first-page":"2564","DOI":"10.3389\/fimmu.2018.02564","volume":"9","author":"JM Ratter","year":"2018","unstructured":"Ratter JM, Rooijackers HMM, Hooiveld GJ, Hijmans AGM, de Galan BE, Tack CJ, Stienstra R (2018) In vitro and in vivo effects of lactate on metabolism and cytokine production of human primary PBMCs and monocytes. Front Immunol 9:2564. https:\/\/doi.org\/10.3389\/fimmu.2018.02564","journal-title":"Front Immunol"},{"key":"5723_CR40","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.cmet.2016.10.015","volume":"24","author":"KE Scott","year":"2016","unstructured":"Scott KE, Cleveland JL (2016) Lactate wreaks havoc on tumor-infiltrating T and NK cells. Cell Metab 24:649\u2013650. https:\/\/doi.org\/10.1016\/j.cmet.2016.10.015","journal-title":"Cell Metab"},{"key":"5723_CR41","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1182\/blood-2018-06-857250","volume":"132","author":"V Shah","year":"2018","unstructured":"Shah V, Johnson DC, Sherborne AL, Ellis S, Aldridge FM, Howard-Reeves J, Begum F, Price A, Kendall J, Chiecchio L, Savola S, Jenner MW, Drayson MT, Owen RG, Gregory WM, Morgan GJ, Davies FE, Houlston RS, Cook G, Cairns DA, Jackson G, Kaiser MF, Group National Cancer Research Institute Haematology Clinical Studies (2018) Subclonal TP53 copy number is associated with prognosis in multiple myeloma. Blood 132:2465\u20132469. https:\/\/doi.org\/10.1182\/blood-2018-06-857250","journal-title":"Blood"},{"key":"5723_CR42","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1038\/s41467-022-29164-0","volume":"13","author":"G Song","year":"2022","unstructured":"Song G, Shi Y, Meng L, Ma J, Huang S, Zhang J, Wu Y, Li J, Lin Y, Yang S, Rao D, Cheng Y, Lin J, Ji S, Liu Y, Jiang S, Wang X, Zhang S, Ke A, Wang X, Cao Y, Ji Y, Zhou J, Fan J, Zhang X, Xi R, Gao Q (2022) Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma. Nat Commun 13:1642. https:\/\/doi.org\/10.1038\/s41467-022-29164-0","journal-title":"Nat Commun"},{"key":"5723_CR43","doi-asserted-by":"publisher","first-page":"503","DOI":"10.14670\/HH-11-819","volume":"32","author":"U Thonsri","year":"2017","unstructured":"Thonsri U, Seubwai W, Waraasawapati S, Sawanyawisuth K, Vaeteewoottacharn K, Boonmars T, Cha\u2019on U (2017) Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis. Histol Histopathol 32:503\u2013510. https:\/\/doi.org\/10.14670\/HH-11-819","journal-title":"Histol Histopathol"},{"key":"5723_CR44","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1136\/gut.2008.157255","volume":"58","author":"CC Thorn","year":"2009","unstructured":"Thorn CC, Freeman TC, Scott N, Guillou PJ, Jayne DG (2009) Laser microdissection expression profiling of marginal edges of colorectal tumours reveals evidence of increased lactate metabolism in the aggressive phenotype. Gut 58:404\u2013412. https:\/\/doi.org\/10.1136\/gut.2008.157255","journal-title":"Gut"},{"key":"5723_CR45","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1159\/000517258","volume":"8","author":"I Tsimafeyeu","year":"2021","unstructured":"Tsimafeyeu I, Temper M (2021) Cholangiocarcinoma: an emerging target for molecular therapy. Gastrointest Tumors 8:153\u2013158. https:\/\/doi.org\/10.1159\/000517258","journal-title":"Gastrointest Tumors"},{"key":"5723_CR46","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.semcancer.2021.05.010","volume":"85","author":"R Ullah","year":"2022","unstructured":"Ullah R, Yin Q, Snell AH, Wan L (2022) RAF-MEK-ERK pathway in cancer evolution and treatment. Semin Cancer Biol 85:123\u2013154. https:\/\/doi.org\/10.1016\/j.semcancer.2021.05.010","journal-title":"Semin Cancer Biol"},{"key":"5723_CR47","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s12935-021-01915-x","volume":"21","author":"Z Wang","year":"2021","unstructured":"Wang Z, Embaye KS, Yang Q, Qin L, Zhang C, Liu L, Zhan X, Zhang F, Wang X, Qin S (2021) Establishment and validation of a prognostic signature for lung adenocarcinoma based on metabolism-related genes. Cancer Cell Int 21:219. https:\/\/doi.org\/10.1186\/s12935-021-01915-x","journal-title":"Cancer Cell Int"},{"issue":"1067\u201381","key":"5723_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.017","volume":"55","author":"Z Wang","year":"2022","unstructured":"Wang Z, Lu Z, Lin S, Xia J, Zhong Z, Xie Z, Xing Y, Qie J, Jiao M, Li Y, Wen H, Zhao P, Zhang D, Zhou P, Qian J, Luo F, Wang L, Yu H, Liu J, Gu J, Liu R, Chu Y (2022) Leucine-tRNA-synthase-2-expressing B cells contribute to colorectal cancer immunoevasion. Immunity 55(1067\u201381):e8. https:\/\/doi.org\/10.1016\/j.immuni.2022.04.017","journal-title":"Immunity"},{"key":"5723_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.874731","volume":"12","author":"L Yang","year":"2022","unstructured":"Yang L, Tan P, Sun H, Zeng Z, Pan Y (2022) Integrative dissection of novel lactate metabolism-related signature in the tumor immune microenvironment and prognostic prediction in breast cancer. Front Oncol 12:874731. https:\/\/doi.org\/10.3389\/fonc.2022.874731","journal-title":"Front Oncol"},{"key":"5723_CR50","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s42255-022-00710-w","volume":"5","author":"Z Yang","year":"2023","unstructured":"Yang Z, Yan C, Ma J, Peng P, Ren X, Cai S, Shen X, Wu Y, Zhang S, Wang X, Qiu S, Zhou J, Fan J, Huang H, Gao Q (2023) Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab 5:61\u201379. https:\/\/doi.org\/10.1038\/s42255-022-00710-w","journal-title":"Nat Metab"},{"key":"5723_CR51","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS"},{"key":"5723_CR52","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1038\/s41590-020-0793-3","volume":"21","author":"YR Yu","year":"2020","unstructured":"Yu YR, Imrichova H, Wang H, Chao T, Xiao Z, Gao M, Rincon-Restrepo M, Franco F, Genolet R, Cheng WC, Jandus C, Coukos G, Jiang YF, Locasale JW, Zippelius A, Liu PS, Tang L, Bock C, Vannini N, Ho PC (2020) Disturbed mitochondrial dynamics in CD8(+) TILs reinforce T cell exhaustion. Nat Immunol 21:1540\u20131551. https:\/\/doi.org\/10.1038\/s41590-020-0793-3","journal-title":"Nat Immunol"},{"key":"5723_CR53","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41419-022-05540-y","volume":"14","author":"X Yu","year":"2023","unstructured":"Yu X, Tong H, Chen J, Tang C, Wang S, Si Y, Wang S, Tang Z (2023) CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export. Cell Death Dis 14:20. https:\/\/doi.org\/10.1038\/s41419-022-05540-y","journal-title":"Cell Death Dis"},{"key":"5723_CR54","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13045-020-00949-4","volume":"13","author":"J Yuan","year":"2020","unstructured":"Yuan J, Dong X, Yap J, Hu J (2020) The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy. J Hematol Oncol 13:113. https:\/\/doi.org\/10.1186\/s13045-020-00949-4","journal-title":"J Hematol Oncol"},{"key":"5723_CR55","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3389\/fonc.2020.01025","volume":"10","author":"B Zhang","year":"2020","unstructured":"Zhang B, Zhou BH, Xiao M, Li H, Guo L, Wang MX, Yu SH, Ye QH (2020) KDM5C represses FASN-mediated lipid metabolism to exert tumor suppressor activity in intrahepatic cholangiocarcinoma. Front Oncol 10:1025. https:\/\/doi.org\/10.3389\/fonc.2020.01025","journal-title":"Front Oncol"},{"key":"5723_CR56","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1158\/2159-8290.CD-23-0282","volume":"13","author":"M Zhang","year":"2023","unstructured":"Zhang M, Huang Y, Pan J, Sang C, Lin Y, Dong L, Shen X, Wu Y, Song G, Ji S, Liu F, Wang M, Zheng Y, Zhang S, Wang Z, Ren J, Gao D, Zhou J, Fan J, Wei W, Lin J, Gao Q (2023) An inflammatory checkpoint generated by IL1RN splicing offers therapeutic opportunity for KRAS-mutant intrahepatic cholangiocarcinoma. Cancer Discov 13:2248\u20132269. https:\/\/doi.org\/10.1158\/2159-8290.CD-23-0282","journal-title":"Cancer Discov"},{"key":"5723_CR57","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13045-020-00852-y","volume":"13","author":"S Zheng","year":"2020","unstructured":"Zheng S, Yang L, Zou Y, Liang JY, Liu P, Gao G, Yang A, Tang H, Xie X (2020) Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer. J Hematol Oncol 13:17. https:\/\/doi.org\/10.1186\/s13045-020-00852-y","journal-title":"J Hematol Oncol"},{"key":"5723_CR58","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523. https:\/\/doi.org\/10.1038\/s41467-019-09234-6","journal-title":"Nat Commun"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05723-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-024-05723-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05723-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T04:09:09Z","timestamp":1716437349000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-024-05723-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["5723"],"URL":"https:\/\/doi.org\/10.1007\/s00432-024-05723-4","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]},"assertion":[{"value":"27 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}],"article-number":"199"}}