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image of Circadian Rhythm Genes-based Prognostic Signature for Bladder Cancer: Association of EZH2 Expression with Anesthetic-related Changes in Circulating Tumor Cells

Abstract

Introduction

Circadian rhythm genes (CRGs) play a significant role in the pathogenesis of various cancers, yet their impact on bladder cancer (BC) remains to be fully elucidated. EZH2, as a potential oncological biomarker, lacks clear delineation regarding its prognostic significance in BC. Furthermore, the effect of anesthesia on circulating tumor cells (CTCs) in cancer patients is scarcely studied.

Method

In this study, we developed a bioinformatics signature based on CRGs to assess the prognosis of BC patients and investigated the expression of EZH2 in BC and its correlation with patient outcomes through clinical sample analysis. Furthermore, we collected blood samples from BC patients before anesthesia and two hours post-anesthesia, enriched for CTCs, and analyzed the expression of EZH2 to evaluate the impact of anesthesia on the quantity of CTCs and their EZH2 expression status.

Results

Our prognostic model identified EZH2 as a key determinant of BC prognosis, with the high expression of EZH2 significantly associated with poor patient outcomes. Experimental validation revealed a significant increase in the number of EZH2+ CTCs after anesthesia in BC patients. These findings suggest that anesthesia may facilitate BC metastasis by increasing the number of EZH2+ CTCs.

Discussion

The findings highlight the prognostic value of CRGs and EZH2 in BC, providing new insights into tumor biology and metastasis. Furthermore, this study suggests anesthesia may influence tumor progression by modulating EZH2 expression in CTCs, underscoring the need for careful anesthetic selection in BC patients.

Conclusion

This study unveils the potential value of CRGs and EZH2 in the prognostic assessment of BC and reports for the first time that anesthesia may influence tumor metastasis by modulating the expression of EZH2 in CTCs. These results offer new biomarkers for the prognosis and treatment of BC and provide novel insights into the role of anesthesia in cancer metastasis.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-07-28
2026-02-23
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References

  1. Siegel R.L. Giaquinto A.N. Jemal A. Cancer statistics, 2024. CA Cancer J. Clin. 2024 74 1 12 49 10.3322/caac.21820 38230766
    [Google Scholar]
  2. Compérat E. Amin M.B. Cathomas R. Choudhury A. De Santis M. Kamat A. Stenzl A. Thoeny H.C. Witjes J.A. Current best practice for bladder cancer: A narrative review of diagnostics and treatments. Lancet 2022 400 10364 1712 1721 10.1016/S0140‑6736(22)01188‑6 36174585
    [Google Scholar]
  3. Kumbham S. Md Mahabubur Rahman K. Foster B.A. You Y. A comprehensive review of current approaches in bladder cancer treatment. ACS Pharmacol. Transl. Sci. 2025 8 2 286 307 10.1021/acsptsci.4c00663 39974639
    [Google Scholar]
  4. Smani S. DuBois J. Zhao K. Sutherland R. Rahman S.N. Humphrey P. Hesse D. Tan W.S. Martin D. Lokeshwar S.D. Ghali F. Advancements in the diagnosis, treatment, and risk stratification of non-muscle invasive bladder cancer. Curr. Oncol. Rep. 2025 10.1007/s11912‑025‑01645‑7 39976835
    [Google Scholar]
  5. Ji J. Wang F. Lai C.H. Wang M. Hu H. Xu K. Xu T. Hu H. Impact of upper tract urothelial carcinoma history on patients with non-muscle invasive bladder cancer undergoing intravesical chemotherapy. Sci. Rep. 2025 15 1 5977 10.1038/s41598‑025‑89525‑9 39966479
    [Google Scholar]
  6. Yu A. Bai Z. Wang Y. Luo Z. Du X. Chen M. Wen S. Wang H. Yuan X. Yang C. Bai S. Fan B. Impact of finasteride on modulating the risk and clinical outcomes of bladder cancer: Insights from a comprehensive meta-analysis. Front. Pharmacol. 2025 16 1471442 10.3389/fphar.2025.1471442 39944628
    [Google Scholar]
  7. Sakaguchi M. Maebayashi T. Sekino Y. Ishikawa H. Efficacy of curative radiotherapy for the treatment of elderly patients with muscle-invasive bladder cancer: A systematic review. BMC Urol. 2025 25 1 26 10.1186/s12894‑025‑01707‑9 39934792
    [Google Scholar]
  8. Ghandour R. Singla N. Lotan Y. Treatment options and outcomes in nonmetastatic muscle invasive bladder cancer. Trends Cancer 2019 5 7 426 439 10.1016/j.trecan.2019.05.011 31311657
    [Google Scholar]
  9. Lenis A.T. Lec P.M. Chamie K. Mshs M. Bladder cancer. JAMA 2020 324 19 1980 1991 10.1001/jama.2020.17598 33201207
    [Google Scholar]
  10. Liatsos G.D. Mariolis I. Hadziyannis E. Bamias A. Vassilopoulos D. Review of BCG immunotherapy for bladder cancer. Clin. Microbiol. Rev. 2025 38 1 e00194-23 Advance online publication 10.1128/cmr.00194‑23 39932308
    [Google Scholar]
  11. Kwon W.A. Seo H.K. Song G. Lee M.K. Park W.S. Advances in therapy for urothelial and non-urothelial subtype histologies of advanced bladder cancer: From etiology to current development. Biomedicines 2025 13 1 86 10.3390/biomedicines13010086 39857670
    [Google Scholar]
  12. Yamashita R. Sugino T. Notsu A. Ito K. Sakura Y. Shinsaka H. Matsuzaki M. Niwakawa M. Kikuchi E. Clinical outcome of BCG treatment for patients with urothelial carcinoma of the prostatic urethra: Implications for early cystectomy. World J. Urol. 2025 43 1 71 10.1007/s00345‑024‑05436‑w 39808304
    [Google Scholar]
  13. Tripathy R. Kumar L. Agarwal S. Thakur A. Khairnar M. Trivedi S. Sankhwar S.N. A comparison between intravesical gemcitabine plus docetaxel and intravesical bacillus calmette-guérin in the treatment of nonmuscle invasive naive urinary bladder cancer: A systematic review and meta-analysis of oncological outcomes. Urology 2025 S0090-4295(25)00006-8 10.1016/j.urology.2025.01.004
    [Google Scholar]
  14. Tortora F. Guastaferro A. Barbato S. Febbraio F. Cimmino A. New challenges in bladder cancer diagnosis: How biosensing tools can lead to population screening opportunities. Sensors 2024 24 24 7873 10.3390/s24247873 39771612
    [Google Scholar]
  15. Dobruch J. Oszczudłowski M. Bladder cancer: Current challenges and future directions. Medicina 2021 57 8 749 10.3390/medicina57080749 34440955
    [Google Scholar]
  16. Meyer N. Harvey A.G. Lockley S.W. Dijk D.J. Circadian rhythms and disorders of the timing of sleep. Lancet 2022 400 10357 1061 1078 10.1016/S0140‑6736(22)00877‑7 36115370
    [Google Scholar]
  17. Zhou L. Zhang Z. Nice E. Huang C. Zhang W. Tang Y. Circadian rhythms and cancers: The intrinsic links and therapeutic potentials. J. Hematol. Oncol. 2022 15 1 21 10.1186/s13045‑022‑01238‑y 35246220
    [Google Scholar]
  18. Kim D.H. Go H.S. Jeon E.J. Nguyen T.Q.T. Kim D.Y. Park H. Eom H.J. Kim S.Y. Park S.C. Cho K.A. The impact of toll-like receptor 5 on liver function in age-related metabolic disorders. Aging Cell 2025 e70009 10.1111/acel.70009 39957532
    [Google Scholar]
  19. Jiménez-Pastor J.M. Morales-Cané I. Rodríguez-Cortés F.J. López-Coleto L. Valverde-León R. Arévalo-Buitrago P. Medina-Valverde M.J. De la Fuente-Martos C. Acuña-Castroviejo D. Meira e Cruz M. Luque R.M. Sarmento-Cabral A. López-Soto P.J. Interaction between clock genes, melatonin and cardiovascular outcomes from ICU patients. Intensive Care Med. Exp. 2025 13 1 19 10.1186/s40635‑025‑00730‑2 39961935
    [Google Scholar]
  20. Zhang H. Li K. Wang Y. Wei C.J. Gao Y.X. Ren-Zhou Zhong Y. Yin Z. Ren D. ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins. Redox Biol. 2025 81 103526 10.1016/j.redox.2025.103526 39952198
    [Google Scholar]
  21. Duez H. Staels B. Circadian disruption and the risk of developing obesity. Curr. Obes. Rep. 2025 14 1 20 10.1007/s13679‑025‑00610‑6 39939483
    [Google Scholar]
  22. Peng L. Jiang M. Li K. Yu S. Zhao C. Zhang L. Li L. Transcriptome profiling revealed multiple circadian rhythm-related genes associated with common gynecological cancers. Front. Oncol. 2025 15 1422122 10.3389/fonc.2025.1422122 39944833
    [Google Scholar]
  23. Olejniczak I. Oster H. Ray D.W. Glucocorticoid circadian rhythms in immune function. Semin. Immunopathol. 2022 44 2 153 163 10.1007/s00281‑021‑00889‑2 34580744
    [Google Scholar]
  24. Bishehsari F. Voigt R.M. Keshavarzian A. Circadian rhythms and the gut microbiota: From the metabolic syndrome to cancer. Nat. Rev. Endocrinol. 2020 16 12 731 739 10.1038/s41574‑020‑00427‑4 33106657
    [Google Scholar]
  25. Lu R. Cai H. Liu Y. Ma G. Wang J. Yan M. Zhang Z. Yu B. Li Z. Fang S. Long non-coding RNA AK023617 orchestrates atherosclerosis by regulating the circadian rhythm of immunity-related GTPase family M protein in macrophages. Noncoding RNA Res. 2025 11 262 272 10.1016/j.ncrna.2024.12.008 39902258
    [Google Scholar]
  26. Li Y.S. Fujihara H. Fujisawa K. Kawai K. Effect of circadian rhythm disruption induced by time-restricted feeding and exercise on oxidative stress and immune in mice. J. Clin. Biochem. Nutr. 2025 76 1 35 41 10.3164/jcbn.24‑126 39896158
    [Google Scholar]
  27. Costa B. Mourão J. Vale N. Personalized medicine for classical anesthesia drugs and cancer progression. J. Pers. Med. 2022 12 11 1846 10.3390/jpm12111846 36579541
    [Google Scholar]
  28. Bezu L. Rahmani L.S. Buggy D.J. The effect of the type of anaesthesia on long-term outcomes after cancer resection surgery: A narrative review. Anaesthesia 2025 80 2 179 187 10.1111/anae.16464 39777733
    [Google Scholar]
  29. Choi H. Hwang W. Anesthetic approaches and their impact on cancer recurrence and metastasis: A comprehensive review. Cancers 2024 16 24 4269 10.3390/cancers16244269 39766169
    [Google Scholar]
  30. Han J.H. Yuk H.D. Jeong S.H. Jeong C.W. Kwak C. Kim J.T. Ku J.H. Anesthetic approaches and 2-year recurrence rates in non-muscle invasive bladder cancer: A randomized clinical trial. Reg. Anesth. Pain Med. 2024 rapm-2024-105949 Advance online publication 10.1136/rapm‑2024‑105949 39740955
    [Google Scholar]
  31. Bezu L. Forget P. Hollmann M.W. Parat M.O. Piegeler T. Potential influence of different peri-operative analgesic regimens on tumour biology and outcome after oncologic surgery. Eur. J. Anaesthesiol. 2025 42 3 233 243 10.1097/EJA.0000000000002118 39743967
    [Google Scholar]
  32. Hoadley K.A. Yau C. Hinoue T. Wolf D.M. Lazar A.J. Drill E. Shen R. Taylor A.M. Cherniack A.D. Thorsson V. Akbani R. Bowlby R. Wong C.K. Wiznerowicz M. Sanchez-Vega F. Robertson A.G. Schneider B.G. Lawrence M.S. Noushmehr H. Malta T.M. Caesar-Johnson S.J. Demchok J.A. Felau I. Kasapi M. Ferguson M.L. Hutter C.M. Sofia H.J. Tarnuzzer R. Wang Z. Yang L. Zenklusen J.C. Zhang J.J. Chudamani S. Liu J. Lolla L. Naresh R. Pihl T. Sun Q. Wan Y. Wu Y. Cho J. DeFreitas T. Frazer S. Gehlenborg N. Getz G. Heiman D.I. Kim J. Lawrence M.S. Lin P. Meier S. Noble M.S. Saksena G. Voet D. Zhang H. Bernard B. Chambwe N. Dhankani V. Knijnenburg T. Kramer R. Leinonen K. Liu Y. Miller M. Reynolds S. Shmulevich I. Thorsson V. Zhang W. Akbani R. Broom B.M. Hegde A.M. Ju Z. Kanchi R.S. Korkut A. Li J. Liang H. Ling S. Liu W. Lu Y. Mills G.B. Ng K-S. Rao A. Ryan M. Wang J. Weinstein J.N. Zhang J. Abeshouse A. Armenia J. Chakravarty D. Chatila W.K. de Bruijn I. Gao J. Gross B.E. Heins Z.J. Kundra R. La K. Ladanyi M. Luna A. Nissan M.G. Ochoa A. Phillips S.M. Reznik E. Sanchez-Vega F. Sander C. Schultz N. Sheridan R. Sumer S.O. Sun Y. Taylor B.S. Wang J. Zhang H. Anur P. Peto M. Spellman P. Benz C. Stuart J.M. Wong C.K. Yau C. Hayes D.N. Parker J.S. Wilkerson M.D. Ally A. Balasundaram M. Bowlby R. Brooks D. Carlsen R. Chuah E. Dhalla N. Holt R. Jones S.J.M. Kasaian K. Lee D. Ma Y. Marra M.A. Mayo M. Moore R.A. Mungall A.J. Mungall K. Robertson A.G. Sadeghi S. Schein J.E. Sipahimalani P. Tam A. Thiessen N. Tse K. Wong T. Berger A.C. Beroukhim R. Cherniack A.D. Cibulskis C. Gabriel S.B. Gao G.F. Ha G. Meyerson M. Schumacher S.E. Shih J. Kucherlapati M.H. Kucherlapati R.S. Baylin S. Cope L. Danilova L. Bootwalla M.S. Lai P.H. Maglinte D.T. Van Den Berg D.J. Weisenberger D.J. Auman J.T. Balu S. Bodenheimer T. Fan C. Hoadley K.A. Hoyle A.P. Jefferys S.R. Jones C.D. Meng S. Mieczkowski P.A. Mose L.E. Perou A.H. Perou C.M. Roach J. Shi Y. Simons J.V. Skelly T. Soloway M.G. Tan D. Veluvolu U. Fan H. Hinoue T. Laird P.W. Shen H. Zhou W. Bellair M. Chang K. Covington K. Creighton C.J. Dinh H. Doddapaneni H.V. Donehower L.A. Drummond J. Gibbs R.A. Glenn R. Hale W. Han Y. Hu J. Korchina V. Lee S. Lewis L. Li W. Liu X. Morgan M. Morton D. Muzny D. Santibanez J. Sheth M. Shinbrot E. Wang L. Wang M. Wheeler D.A. Xi L. Zhao F. Hess J. Appelbaum E.L. Bailey M. Cordes M.G. Ding L. Fronick C.C. Fulton L.A. Fulton R.S. Kandoth C. Mardis E.R. McLellan M.D. Miller C.A. Schmidt H.K. Wilson R.K. Crain D. Curley E. Gardner J. Lau K. Mallery D. Morris S. Paulauskis J. Penny R. Shelton C. Shelton T. Sherman M. Thompson E. Yena P. Bowen J. Gastier-Foster J.M. Gerken M. Leraas K.M. Lichtenberg T.M. Ramirez N.C. Wise L. Zmuda E. Corcoran N. Costello T. Hovens C. Carvalho A.L. de Carvalho A.C. Fregnani J.H. Longatto-Filho A. Reis R.M. Scapulatempo-Neto C. Silveira H.C.S. Vidal D.O. Burnette A. Eschbacher J. Hermes B. Noss A. Singh R. Anderson M.L. Castro P.D. Ittmann M. Huntsman D. Kohl B. Le X. Thorp R. Andry C. Duffy E.R. Lyadov V. Paklina O. Setdikova G. Shabunin A. Tavobilov M. McPherson C. Warnick R. Berkowitz R. Cramer D. Feltmate C. Horowitz N. Kibel A. Muto M. Raut C.P. Malykh A. Barnholtz-Sloan J.S. Barrett W. Devine K. Fulop J. Ostrom Q.T. Shimmel K. Wolinsky Y. Sloan A.E. De Rose A. Giuliante F. Goodman M. Karlan B.Y. Hagedorn C.H. Eckman J. Harr J. Myers J. Tucker K. Zach L.A. Deyarmin B. Hu H. Kvecher L. Larson C. Mural R.J. Somiari S. Vicha A. Zelinka T. Bennett J. Iacocca M. Rabeno B. Swanson P. Latour M. Lacombe L. Têtu B. Bergeron A. McGraw M. Staugaitis S.M. Chabot J. Hibshoosh H. Sepulveda A. Su T. Wang T. Potapova O. Voronina O. Desjardins L. Mariani O. Roman-Roman S. Sastre X. Stern M-H. Cheng F. Signoretti S. Berchuck A. Bigner D. Lipp E. Marks J. McCall S. McLendon R. Secord A. Sharp A. Behera M. Brat D.J. Chen A. Delman K. Force S. Khuri F. Magliocca K. Maithel S. Olson J.J. Owonikoko T. Pickens A. Ramalingam S. Shin D.M. Sica G. Van Meir E.G. Zhang H. Eijckenboom W. Gillis A. Korpershoek E. Looijenga L. Oosterhuis W. Stoop H. van Kessel K.E. Zwarthoff E.C. Calatozzolo C. Cuppini L. Cuzzubbo S. DiMeco F. Finocchiaro G. Mattei L. Perin A. Pollo B. Chen C. Houck J. Lohavanichbutr P. Hartmann A. Stoehr C. Stoehr R. Taubert H. Wach S. Wullich B. Kycler W. Murawa D. Wiznerowicz M. Chung K. Edenfield W.J. Martin J. Baudin E. Bubley G. Bueno R. De Rienzo A. Richards W.G. Kalkanis S. Mikkelsen T. Noushmehr H. Scarpace L. Girard N. Aymerich M. Campo E. Giné E. Guillermo A.L. Van Bang N. Hanh P.T. Phu B.D. Tang Y. Colman H. Evason K. Dottino P.R. Martignetti J.A. Gabra H. Juhl H. Akeredolu T. Stepa S. Hoon D. Ahn K. Kang K.J. Beuschlein F. Breggia A. Birrer M. Bell D. Borad M. Bryce A.H. Castle E. Chandan V. Cheville J. Copland J.A. Farnell M. Flotte T. Giama N. Ho T. Kendrick M. Kocher J-P. Kopp K. Moser C. Nagorney D. O’Brien D. O’Neill B.P. Patel T. Petersen G. Que F. Rivera M. Roberts L. Smallridge R. Smyrk T. Stanton M. Thompson R.H. Torbenson M. Yang J.D. Zhang L. Brimo F. Ajani J.A. Gonzalez A.M.A. Behrens C. Bondaruk Broaddus R. Czerniak B. Esmaeli B. Fujimoto J. Gershenwald J. Guo C. Lazar A.J. Logothetis C. Meric-Bernstam F. Moran C. Ramondetta L. Rice D. Sood A. Tamboli P. Thompson T. Troncoso P. Tsao A. Wistuba I. Carter C. Haydu L. Hersey P. Jakrot V. Kakavand H. Kefford R. Lee K. Long G. Mann G. Quinn M. Saw R. Scolyer R. Shannon K. Spillane A. Stretch J. Synott M. Thompson J. Wilmott J. Al-Ahmadie H. Chan T.A. Ghossein R. Gopalan A. Levine D.A. Reuter V. Singer S. Singh B. Tien N.V. Broudy T. Mirsaidi C. Nair P. Drwiega P. Miller J. Smith J. Zaren H. Park J-W. Hung N.P. Kebebew E. Linehan W.M. Metwalli A.R. Pacak K. Pinto P.A. Schiffman M. Schmidt L.S. Vocke C.D. Wentzensen N. Worrell R. Yang H. Moncrieff M. Goparaju C. Melamed J. Pass H. Botnariuc N. Caraman I. Cernat M. Chemencedji I. Clipca A. Doruc S. Gorincioi G. Mura S. Pirtac M. Stancul I. Tcaciuc D. Albert M. Alexopoulou I. Arnaout A. Bartlett J. Engel J. Gilbert S. Parfitt J. Sekhon H. Thomas G. Rassl D.M. Rintoul R.C. Bifulco C. Tamakawa R. Urba W. Hayward N. Timmers H. Antenucci A. Facciolo F. Grazi G. Marino M. Merola R. de Krijger R. Gimenez-Roqueplo A-P. Piché A. Chevalier S. McKercher G. Birsoy K. Barnett G. Brewer C. Farver C. Naska T. Pennell N.A. Raymond D. Schilero C. Smolenski K. Williams F. Morrison C. Borgia J.A. Liptay M.J. Pool M. Seder C.W. Junker K. Omberg L. Dinkin M. Manikhas G. Alvaro D. Bragazzi M.C. Cardinale V. Carpino G. Gaudio E. Chesla D. Cottingham S. Dubina M. Moiseenko F. Dhanasekaran R. Becker K-F. Janssen K-P. Slotta-Huspenina J. Abdel-Rahman M.H. Aziz D. Bell S. Cebulla C.M. Davis A. Duell R. Elder J.B. Hilty J. Kumar B. Lang J. Lehman N.L. Mandt R. Nguyen P. Pilarski R. Rai K. Schoenfield L. Senecal K. Wakely P. Hansen P. Lechan R. Powers J. Tischler A. Grizzle W.E. Sexton K.C. Kastl A. Henderson J. Porten S. Waldmann J. Fassnacht M. Asa S.L. Schadendorf D. Couce M. Graefen M. Huland H. Sauter G. Schlomm T. Simon R. Tennstedt P. Olabode O. Nelson M. Bathe O. Carroll P.R. Chan J.M. Disaia P. Glenn P. Kelley R.K. Landen C.N. Phillips J. Prados M. Simko J. Smith-McCune K. VandenBerg S. Roggin K. Fehrenbach A. Kendler A. Sifri S. Steele R. Jimeno A. Carey F. Forgie I. Mannelli M. Carney M. Hernandez B. Campos B. Herold-Mende C. Jungk C. Unterberg A. von Deimling A. Bossler A. Galbraith J. Jacobus L. Knudson M. Knutson T. Ma D. Milhem M. Sigmund R. Godwin A.K. Madan R. Rosenthal H.G. Adebamowo C. Adebamowo S.N. Boussioutas A. Beer D. Giordano T. Mes-Masson A-M. Saad F. Bocklage T. Landrum L. Mannel R. Moore K. Moxley K. Postier R. Walker J. Zuna R. Feldman M. Valdivieso F. Dhir R. Luketich J. Pinero E.M.M. Quintero-Aguilo M. Carlotti C.G. Jr Dos Santos J.S. Kemp R. Sankarankuty A. Tirapelli D. Catto J. Agnew K. Swisher E. Creaney J. Robinson B. Shelley C.S. Godwin E.M. Kendall S. Shipman C. Bradford C. Carey T. Haddad A. Moyer J. Peterson L. Prince M. Rozek L. Wolf G. Bowman R. Fong K.M. Yang I. Korst R. Rathmell W.K. Fantacone-Campbell J.L. Hooke J.A. Kovatich A.J. Shriver C.D. DiPersio J. Drake B. Govindan R. Heath S. Ley T. Van Tine B. Westervelt P. Rubin M.A. Lee J.I. Aredes N.D. Mariamidze A. Stuart J.M. Benz C.C. Laird P.W. Cancer Genome Atlas Network Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 2018 173 2 291 304.e6 10.1016/j.cell.2018.03.022 29625048
    [Google Scholar]
  33. Wu Y. Shen C. Wang X. Zhao W. Li Y. He X. Chen Y. Liu J. Wu X. Shen A. Development and validation of a novel circadian rhythm-related signature to predict the prognosis of the patients with hepatocellular carcinoma. BioMed Res. Int. 2022 2022 1 4263261 10.1155/2022/4263261 35993051
    [Google Scholar]
  34. Kanehisa M. Furumichi M. Sato Y. Matsuura Y. Ishiguro-Watanabe M. KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. 2025 53 D1 D672 D677 10.1093/nar/gkae909 39417505
    [Google Scholar]
  35. Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019 28 11 1947 1951 10.1002/pro.3715 31441146
    [Google Scholar]
  36. Kanehisa M. Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000 28 1 27 30 10.1093/nar/28.1.27
    [Google Scholar]
  37. Hänzelmann S. Castelo R. Guinney J. GSVA: Gene set variation analysis for microarray and RNA-Seq data. BMC Bioinformatics 2013 14 1 7 10.1186/1471‑2105‑14‑7 23323831
    [Google Scholar]
  38. Lee E. Chuang H.Y. Kim J.W. Ideker T. Lee D. Inferring pathway activity toward precise disease classification. PLOS Comput. Biol. 2008 4 11 e1000217 10.1371/journal.pcbi.1000217 18989396
    [Google Scholar]
  39. Van Calster B. Wynants L. Verbeek J.F.M. Verbakel J.Y. Christodoulou E. Vickers A.J. Roobol M.J. Steyerberg E.W. Reporting and interpreting decision curve analysis: A guide for investigators. Eur. Urol. 2018 74 6 796 804 10.1016/j.eururo.2018.08.038 30241973
    [Google Scholar]
  40. Lee C. Kim H. Machine learning-based predictive modeling of depression in hypertensive populations. PLoS One 2022 17 7 e0272330 10.1371/journal.pone.0272330 35905087
    [Google Scholar]
  41. Bindea G. Mlecnik B. Tosolini M. Kirilovsky A. Waldner M. Obenauf A.C. Angell H. Fredriksen T. Lafontaine L. Berger A. Bruneval P. Fridman W.H. Becker C. Pagès F. Speicher M.R. Trajanoski Z. Galon J. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013 39 4 782 795 10.1016/j.immuni.2013.10.003 24138885
    [Google Scholar]
  42. Ru B. Wong C.N. Tong Y. Zhong J.Y. Zhong S.S.W. Wu W.C. Chu K.C. Wong C.Y. Lau C.Y. Chen I. Chan N.W. Zhang J. TISIDB: An integrated repository portal for tumor–immune system interactions. Bioinformatics 2019 35 20 4200 4202 10.1093/bioinformatics/btz210 30903160
    [Google Scholar]
  43. Thorsson V. Gibbs D.L. Brown S.D. Wolf D. Bortone D.S. Ou Yang T.H. Porta-Pardo E. Gao G.F. Plaisier C.L. Eddy J.A. Ziv E. Culhane A.C. Paull E.O. Sivakumar I.K.A. Gentles A.J. Malhotra R. Farshidfar F. Colaprico A. Parker J.S. Mose L.E. Vo N.S. Liu J. Liu Y. Rader J. Dhankani V. Reynolds S.M. Bowlby R. Califano A. Cherniack A.D. Anastassiou D. Bedognetti D. Mokrab Y. Newman A.M. Rao A. Chen K. Krasnitz A. Hu H. Malta T.M. Noushmehr H. Pedamallu C.S. Bullman S. Ojesina A.I. Lamb A. Zhou W. Shen H. Choueiri T.K. Weinstein J.N. Guinney J. Saltz J. Holt R.A. Rabkin C.S. Lazar A.J. Serody J.S. Demicco E.G. Disis M.L. Vincent B.G. Shmulevich I. Caesar-Johnson S.J. Demchok J.A. Felau I. Kasapi M. Ferguson M.L. Hutter C.M. Sofia H.J. Tarnuzzer R. Wang Z. Yang L. Zenklusen J.C. Zhang J.J. Chudamani S. Liu J. Lolla L. Naresh R. Pihl T. Sun Q. Wan Y. Wu Y. Cho J. DeFreitas T. Frazer S. Gehlenborg N. Getz G. Heiman D.I. Kim J. Lawrence M.S. Lin P. Meier S. Noble M.S. Saksena G. Voet D. Zhang H. Bernard B. Chambwe N. Dhankani V. Knijnenburg T. Kramer R. Leinonen K. Liu Y. Miller M. Reynolds S. Shmulevich I. Thorsson V. Zhang W. Akbani R. Broom B.M. Hegde A.M. Ju Z. Kanchi R.S. Korkut A. Li J. Liang H. Ling S. Liu W. Lu Y. Mills G.B. Ng K-S. Rao A. Ryan M. Wang J. Weinstein J.N. Zhang J. Abeshouse A. Armenia J. Chakravarty D. Chatila W.K. de Bruijn I. Gao J. Gross B.E. Heins Z.J. Kundra R. La K. Ladanyi M. Luna A. Nissan M.G. Ochoa A. Phillips S.M. Reznik E. Sanchez-Vega F. Sander C. Schultz N. Sheridan R. Sumer S.O. Sun Y. Taylor B.S. Wang J. Zhang H. Anur P. Peto M. Spellman P. Benz C. Stuart J.M. Wong C.K. Yau C. Hayes D.N. Parker J.S. Wilkerson M.D. Ally A. Balasundaram M. Bowlby R. Brooks D. Carlsen R. Chuah E. Dhalla N. Holt R. Jones S.J.M. Kasaian K. Lee D. Ma Y. Marra M.A. Mayo M. Moore R.A. Mungall A.J. Mungall K. Robertson A.G. Sadeghi S. Schein J.E. Sipahimalani P. Tam A. Thiessen N. Tse K. Wong T. Berger A.C. Beroukhim R. Cherniack A.D. Cibulskis C. Gabriel S.B. Gao G.F. Ha G. Meyerson M. Schumacher S.E. Shih J. Kucherlapati M.H. Kucherlapati R.S. Baylin S. Cope L. Danilova L. Bootwalla M.S. Lai P.H. Maglinte D.T. Van Den Berg D.J. Weisenberger D.J. Auman J.T. Balu S. Bodenheimer T. Fan C. Hoadley K.A. Hoyle A.P. Jefferys S.R. Jones C.D. Meng S. Mieczkowski P.A. Mose L.E. Perou A.H. Perou C.M. Roach J. Shi Y. Simons J.V. Skelly T. Soloway M.G. Tan D. Veluvolu U. Fan H. Hinoue T. Laird P.W. Shen H. Zhou W. Bellair M. Chang K. Covington K. Creighton C.J. Dinh H. Doddapaneni H.V. Donehower L.A. Drummond J. Gibbs R.A. Glenn R. Hale W. Han Y. Hu J. Korchina V. Lee S. Lewis L. Li W. Liu X. Morgan M. Morton D. Muzny D. Santibanez J. Sheth M. Shinbrot E. Wang L. Wang M. Wheeler D.A. Xi L. Zhao F. Hess J. Appelbaum E.L. Bailey M. Cordes M.G. Ding L. Fronick C.C. Fulton L.A. Fulton R.S. Kandoth C. Mardis E.R. McLellan M.D. Miller C.A. Schmidt H.K. Wilson R.K. Crain D. Curley E. Gardner J. Lau K. Mallery D. Morris S. Paulauskis J. Penny R. Shelton C. Shelton T. Sherman M. Thompson E. Yena P. Bowen J. Gastier-Foster J.M. Gerken M. Leraas K.M. Lichtenberg T.M. Ramirez N.C. Wise L. Zmuda E. Corcoran N. Costello T. Hovens C. Carvalho A.L. de Carvalho A.C. Fregnani J.H. Longatto-Filho A. Reis R.M. Scapulatempo-Neto C. Silveira H.C.S. Vidal D.O. Burnette A. Eschbacher J. Hermes B. Noss A. Singh R. Anderson M.L. Castro P.D. Ittmann M. Huntsman D. Kohl B. Le X. Thorp R. Andry C. Duffy E.R. Lyadov V. Paklina O. Setdikova G. Shabunin A. Tavobilov M. McPherson C. Warnick R. Berkowitz R. Cramer D. Feltmate C. Horowitz N. Kibel A. Muto M. Raut C.P. Malykh A. Barnholtz-Sloan J.S. Barrett W. Devine K. Fulop J. Ostrom Q.T. Shimmel K. Wolinsky Y. Sloan A.E. De Rose A. Giuliante F. Goodman M. Karlan B.Y. Hagedorn C.H. Eckman J. Harr J. Myers J. Tucker K. Zach L.A. Deyarmin B. Hu H. Kvecher L. Larson C. Mural R.J. Somiari S. Vicha A. Zelinka T. Bennett J. Iacocca M. Rabeno B. Swanson P. Latour M. Lacombe L. Têtu B. Bergeron A. McGraw M. Staugaitis S.M. Chabot J. Hibshoosh H. Sepulveda A. Su T. Wang T. Potapova O. Voronina O. Desjardins L. Mariani O. Roman-Roman S. Sastre X. Stern M-H. Cheng F. Signoretti S. Berchuck A. Bigner D. Lipp E. Marks J. McCall S. McLendon R. Secord A. Sharp A. Behera M. Brat D.J. Chen A. Delman K. Force S. Khuri F. Magliocca K. Maithel S. Olson J.J. Owonikoko T. Pickens A. Ramalingam S. Shin D.M. Sica G. Van Meir E.G. Zhang H. Eijckenboom W. Gillis A. Korpershoek E. Looijenga L. Oosterhuis W. Stoop H. van Kessel K.E. Zwarthoff E.C. Calatozzolo C. Cuppini L. Cuzzubbo S. DiMeco F. Finocchiaro G. Mattei L. Perin A. Pollo B. Chen C. Houck J. Lohavanichbutr P. Hartmann A. Stoehr C. Stoehr R. Taubert H. Wach S. Wullich B. Kycler W. Murawa D. Wiznerowicz M. Chung K. Edenfield W.J. Martin J. Baudin E. Bubley G. Bueno R. De Rienzo A. Richards W.G. Kalkanis S. Mikkelsen T. Noushmehr H. Scarpace L. Girard N. Aymerich M. Campo E. Giné E. Guillermo A.L. Van Bang N. Hanh P.T. Phu B.D. Tang Y. Colman H. Evason K. Dottino P.R. Martignetti J.A. Gabra H. Juhl H. Akeredolu T. Stepa S. Hoon D. Ahn K. Kang K.J. Beuschlein F. Breggia A. Birrer M. Bell D. Borad M. Bryce A.H. Castle E. Chandan V. Cheville J. Copland J.A. Farnell M. Flotte T. Giama N. Ho T. Kendrick M. Kocher J-P. Kopp K. Moser C. Nagorney D. O’Brien D. O’Neill B.P. Patel T. Petersen G. Que F. Rivera M. Roberts L. Smallridge R. Smyrk T. Stanton M. Thompson R.H. Torbenson M. Yang J.D. Zhang L. Brimo F. Ajani J.A. Gonzalez A.M.A. Behrens C. Bondaruk J. Broaddus R. Czerniak B. Esmaeli B. Fujimoto J. Gershenwald J. Guo C. Lazar A.J. Logothetis C. Meric-Bernstam F. Moran C. Ramondetta L. Rice D. Sood A. Tamboli P. Thompson T. Troncoso P. Tsao A. Wistuba I. Carter C. Haydu L. Hersey P. Jakrot V. Kakavand H. Kefford R. Lee K. Long G. Mann G. Quinn M. Saw R. Scolyer R. Shannon K. Spillane A. Stretch Synott M. Thompson J. Wilmott J. Al-Ahmadie H. Chan T.A. Ghossein R. Gopalan A. Levine D.A. Reuter V. Singer S. Singh B. Tien N.V. Broudy T. Mirsaidi C. Nair P. Drwiega P. Miller J. Smith J. Zaren H. Park J-W. Hung N.P. Kebebew E. Linehan W.M. Metwalli A.R. Pacak K. Pinto P.A. Schiffman M. Schmidt L.S. Vocke C.D. Wentzensen N. Worrell R. Yang H. Moncrieff M. Goparaju C. Melamed J. Pass H. Botnariuc N. Caraman I. Cernat M. Chemencedji I. Clipca A. Doruc S. Gorincioi G. Mura S. Pirtac M. Stancul I. Tcaciuc D. Albert M. Alexopoulou I. Arnaout A. Bartlett J. Engel J. Gilbert S. Parfitt J. Sekhon H. Thomas G. Rassl D.M. Rintoul R.C. Bifulco C. Tamakawa R. Urba W. Hayward N. Timmers H. Antenucci A. Facciolo F. Grazi G. Marino M. Merola R. de Krijger R. Gimenez-Roqueplo A-P. Piché A. Chevalier S. McKercher G. Birsoy K. Barnett G. Brewer C. Farver C. Naska T. Pennell N.A. Raymond D. Schilero C. Smolenski K. Williams F. Morrison C. Borgia J.A. Liptay M.J. Pool M. Seder C.W. Junker K. Omberg L. Dinkin M. Manikhas G. Alvaro D. Bragazzi M.C. Cardinale V. Carpino G. Gaudio E. Chesla D. Cottingham S. Dubina M. Moiseenko F. Dhanasekaran R. Becker K-F. Janssen K-P. Slotta-Huspenina J. Abdel-Rahman M.H. Aziz D. Bell S. Cebulla C.M. Davis A. Duell R. Elder J.B. Hilty J. Kumar B. Lang J. Lehman N.L. Mandt R. Nguyen P. Pilarski R. Rai K. Schoenfield L. Senecal K. Wakely P. Hansen P. Lechan R. Powers J. Tischler A. Grizzle W.E. Sexton K.C. Kastl A. Henderson J. Porten S. Waldmann J. Fassnacht M. Asa S.L. Schadendorf D. Couce M. Graefen M. Huland H. Sauter G. Schlomm T. Simon R. Tennstedt P. Olabode O. Nelson M. Bathe O. Carroll P.R. Chan J.M. Disaia P. Glenn P. Kelley R.K. Landen C.N. Phillips J. Prados M. Simko J. Smith-McCune K. VandenBerg S. Roggin K. Fehrenbach A. Kendler A. Sifri S. Steele R. Jimeno A. Carey F. Forgie I. Mannelli M. Carney M. Hernandez B. Campos B. Herold-Mende C. Jungk C. Unterberg A. von Deimling A. Bossler A. Galbraith J. Jacobus L. Knudson M. Knutson T. Ma D. Milhem M. Sigmund R. Godwin A.K. Madan R. Rosenthal H.G. Adebamowo C. Adebamowo S.N. Boussioutas A. Beer D. Giordano T. Mes-Masson A-M. Saad F. Bocklage T. Landrum L. Mannel R. Moore K. Moxley K. Postier R. Walker J. Zuna R. Feldman M. Valdivieso F. Dhir R. Luketich J. Pinero E.M.M. Quintero-Aguilo M. Carlotti C.G. Jr Dos Santos J.S. Kemp R. Sankarankuty A. Tirapelli D. Catto J. Agnew K. Swisher E. Creaney J. Robinson B. Shelley C.S. Godwin E.M. Kendall S. Shipman C. Bradford C. Carey T. Haddad A. Moyer J. Peterson L. Prince M. Rozek L. Wolf G. Bowman R. Fong K.M. Yang I. Korst R. Rathmell W.K. Fantacone-Campbell J.L. Hooke J.A. Kovatich A.J. Shriver C.D. DiPersio J. Drake B. Govindan R. Heath S. Ley T. Van Tine B. Westervelt P. Rubin M.A. Lee J.I. Aredes N.D. Mariamidze A. Cancer Genome Atlas Research Network The immune landscape of cancer. Immunity 2018 48 4 812 830.e14 10.1016/j.immuni.2018.03.023 29628290
    [Google Scholar]
  44. Teng C. Lu W. Che J. Wu Y. Meng D. Shan Y. Association of pro-inflammatory diet, smoking, and alcohol consumption with bladder cancer: Evidence from case–control and NHANES studies from 1999 to 2020. Nutrients 2024 16 11 1793 10.3390/nu16111793 38892724
    [Google Scholar]
  45. Li J. Deng Z. Soerensen S. J. C. Kachuri L. Cardenas A. Graff R. E. Leppert J. T. Langston M. E. Chung B. I. Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence. Nat. Commun. 2024 15 1 5116 5116 10.1038/s41467‑024‑48857
    [Google Scholar]
  46. Zaghloul M.S. Alnagmy A.K. Kasem H.A. Hakim M.M.A. Abdallah A. Kamal M. Mostafa A.G. Zaghloul T.M. The value and safety of adjuvant radiation therapy after radical cystectomy in locally advanced urothelial bladder cancer: A controlled randomized study. Int. J. Radiat. Oncol. Biol. Phys. 2024 120 3 658 666 10.1016/j.ijrobp.2024.05.012 38879088
    [Google Scholar]
  47. Ranganathan S. Riveros C. Xu J. Hu S. Geng M. Huang E. Melchiode Z. Zhang J. Efstathiou E. Chan K.S. Wallis C.J.D. Sonpavde G. Satkunasivam R. Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience. Urol. Oncol. 2024 42 9 291.e13 291.e25 10.1016/j.urolonc.2024.04.006 38763801
    [Google Scholar]
  48. Wang X.L. Wang Y.X. Chen J.Z. Liu X.Y. Liu X. Zhong Q.K. Zhao Z.L. Shi Z.D. Han C.H. Clinical characteristics and molecular mechanisms underlying bladder cancer in individuals with spinal cord injury: A systematic review. BMC Urol. 2024 24 1 111 10.1186/s12894‑024‑01457‑0 38778291
    [Google Scholar]
  49. Balachandran D.D. Bashoura L. Sheshadri A. Manzullo E. Faiz S.A. The impact of immunotherapy on sleep and circadian rhythms in patients with cancer. Front. Oncol. 2023 13 1295267 10.3389/fonc.2023.1295267 38090501
    [Google Scholar]
  50. Miro C. Docimo A. Barrea L. Verde L. Cernea S. Sojat A.S. Marina L.V. Docimo G. Colao A. Dentice M. Muscogiuri G. “Time” for obesity-related cancer: The role of the circadian rhythm in cancer pathogenesis and treatment. Semin. Cancer Biol. 2023 91 99 109 10.1016/j.semcancer.2023.03.003 36893964
    [Google Scholar]
  51. Peng Y. Chen Y. Chen S. Wang J. Jiang C. Hou W. Xu C. JUND-dependent up-regulation of HMOX1 is associated with cisplatin resistance in muscle-invasive bladder cancer. J. Biochem. 2020 168 1 73 82 10.1093/jb/mvaa027 32240302
    [Google Scholar]
  52. Pan W. Han J. Wei N. Wu H. Wang Y. Sun J. LINC00702-mediated DUSP1 transcription in the prevention of bladder cancer progression: Implications in cancer cell proliferation and tumor inflammatory microenvironment. Genomics 2022 114 4 110428 10.1016/j.ygeno.2022.110428 35809838
    [Google Scholar]
  53. Verma A. Singh A. Singh M.P. Nengroo M.A. Saini K.K. Satrusal S.R. Khan M.A. Chaturvedi P. Sinha A. Meena S. Singh A.K. Datta D. EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis. Nat. Commun. 2022 13 1 7344 10.1038/s41467‑022‑35059‑x 36446780
    [Google Scholar]
  54. Liu Y. Yang Q. The roles of EZH2 in cancer and its inhibitors. Med. Oncol. 2023 40 6 167 10.1007/s12032‑023‑02025‑6 37148376
    [Google Scholar]
  55. Zeng J. Zhang J. Sun Y. Wang J. Ren C. Banerjee S. Ouyang L. Wang Y. Targeting EZH2 for cancer therapy: From current progress to novel strategies. Eur. J. Med. Chem. 2022 238 114419 10.1016/j.ejmech.2022.114419 35569264
    [Google Scholar]
  56. Rinke J. Chase A. Cross N.C.P. Hochhaus A. Ernst T. EZH2 in myeloid malignancies. Cells 2020 9 7 1639 10.3390/cells9071639 32650416
    [Google Scholar]
  57. Wang B. Liu Y. Liao Z. Wu H. Zhang B. Zhang L. EZH2 in hepatocellular carcinoma: Progression, immunity, and potential targeting therapies. Exp. Hematol. Oncol. 2023 12 1 52 10.1186/s40164‑023‑00405‑2 37268997
    [Google Scholar]
  58. Gao J. Fosbrook C. Gibson J. Underwood T.J. Gray J.C. Walters Z.S. Review: Targeting EZH2 in neuroblastoma. Cancer Treat. Rev. 2023 119 102600 10.1016/j.ctrv.2023.102600 37467626
    [Google Scholar]
  59. Xu F. Xu X. Deng H. Yu Z. Huang J. Deng L. Chao H. The role of deubiquitinase USP2 in driving bladder cancer progression by stabilizing EZH2 to epigenetically silence SOX1 expression. Transl. Oncol. 2024 49 102104 10.1016/j.tranon.2024.102104 39197387
    [Google Scholar]
  60. Vantaku V. Putluri V. Bader D.A. Maity S. Ma J. Arnold J.M. Rajapakshe K. Donepudi S.R. von Rundstedt F.C. Devarakonda V. Dubrulle J. Karanam B. McGuire S.E. Stossi F. Jain A.K. Coarfa C. Cao Q. Sikora A.G. Villanueva H. Kavuri S.M. Lotan Y. Sreekumar A. Putluri N. Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression. Oncogene 2020 39 40 6265 6285 10.1038/s41388‑019‑0902‑7 31383940
    [Google Scholar]
  61. Printezi M.I. Kilgallen A.B. Bond M.J.G. Štibler U. Putker M. Teske A.J. Cramer M.J. Punt C.J.A. Sluijter J.P.G. Huitema A.D.R. May A.M. van Laake L.W. Toxicity and efficacy of chronomodulated chemotherapy: A systematic review. Lancet Oncol. 2022 23 3 e129 e143 10.1016/S1470‑2045(21)00639‑2 35240088
    [Google Scholar]
  62. Lévi F. Zidani R. Misset J.L. International Organization for Cancer Chronotherapy Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 1997 350 9079 681 686 10.1016/S0140‑6736(97)03358‑8 9291901
    [Google Scholar]
  63. von Roemeling R. Hrushesky W.J. Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer. J. Clin. Oncol. 1989 7 11 1710 1719 10.1200/JCO.1989.7.11.1710 2530318
    [Google Scholar]
  64. Innominato P.F. Karaboué A. Bouchahda M. Bjarnason G.A. Lévi F.A. The future of precise cancer chronotherapeutics. Lancet Oncol. 2022 23 6 e242 10.1016/S1470‑2045(22)00188‑7 35654059
    [Google Scholar]
  65. Wang C. Barnoud C. Cenerenti M. Sun M. Caffa I. Kizil B. Bill R. Liu Y. Pick R. Garnier L. Gkountidi O.A. Ince L.M. Holtkamp S. Fournier N. Michielin O. Speiser D.E. Hugues S. Nencioni A. Pittet M.J. Jandus C. Scheiermann C. Dendritic cells direct circadian anti-tumour immune responses. Nature 2023 614 7946 136 143 10.1038/s41586‑022‑05605‑0 36470303
    [Google Scholar]
  66. Cata J.P. Sood A.K. Eltzschig H.K. Anesthetic drugs and cancer progression. Anesthesiology 2020 133 4 698 699 10.1097/ALN.0000000000003510 32833387
    [Google Scholar]
  67. Niwa H. Rowbotham D.J. Lambert D.G. Buggy D.J. Can anesthetic techniques or drugs affect cancer recurrence in patients undergoing cancer surgery? J. Anesth. 2013 27 5 731 741 10.1007/s00540‑013‑1615‑7 23670802
    [Google Scholar]
  68. Kim R. Anesthetic technique for cancer surgery: Harm or benefit for cancer recurrence? Eur. J. Surg. Oncol. 2018 44 5 557 558 10.1016/j.ejso.2018.02.207 29530344
    [Google Scholar]
  69. Byrne K. Levins K.J. Buggy D.J. Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis? Can. J. Anaesth. 2016 63 2 184 192 10.1007/s12630‑015‑0523‑8 26497721
    [Google Scholar]
  70. McIlvried L.A. Martel Matos A.A. Yuan M.M. Atherton M.A. Obuekwe F. Nilsen M.L. Nikpoor A.R. Talbot S. Bruno T.C. Taggart D.N. Johnson L.K. Ferris R.L. P Zandberg D. Scheff N.N. Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma. J. Immunother. Cancer 2024 12 11 e009962 10.1136/jitc‑2024‑009962 39551606
    [Google Scholar]
  71. Wang R. Li S. Wang B. Wang G. Zheng H. Impact of opioids and mu-opioid receptors on oncologic metastasis. Am. J. Cancer Res. 2024 14 9 4236 4247 10.62347/SCLS3277 39417177
    [Google Scholar]
  72. Liu Q. Sheng Z. Cheng C. Zheng H. Lanuti M. Liu R. Wang P. Shen Y. Xie Z. Anesthetic propofol promotes tumor metastasis in lungs via GABA A r-dependent TRIM21 modulation of Src expression. Adv. Sci. 2021 8 18 2102079 10.1002/advs.202102079 34263559
    [Google Scholar]
  73. Kadota K. Iijima N. Ohe-Hayashi Y. Takumi K. Higo S. Sakamoto A. Ozawa H. Time-dependent repression of mPer2 expression in the suprachiasmatic nucleus by inhalation anesthesia with sevoflurane. Neurosci. Lett. 2012 528 2 153 158 10.1016/j.neulet.2012.07.061 22902991
    [Google Scholar]
  74. Mihara T. Kikuchi T. Kamiya Y. Koga M. Uchimoto K. Kurahashi K. Goto T. Day or night administration of ketamine and pentobarbital differentially affect circadian rhythms of pineal melatonin secretion and locomotor activity in rats. Anesth. Analg. 2012 115 4 805 813 10.1213/ANE.0b013e3182632bcb 22886841
    [Google Scholar]
  75. Poulsen R.C. Warman G.R. Sleigh J. Ludin N.M. Cheeseman J.F. How does general anaesthesia affect the circadian clock? Sleep Med. Rev. 2018 37 35 44 10.1016/j.smrv.2016.12.002 28162920
    [Google Scholar]
  76. Song B. Li Y. Teng X. Li X. Yang Y. Zhu J. Comparison of morning and evening operation under general anesthesia on intraoperative anesthetic requirement, postoperative sleep quality, and pain: A randomized controlled trial. Nat. Sci. Sleep 2020 12 467 475 10.2147/NSS.S257896 32765143
    [Google Scholar]
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  • Article Type:
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Keywords: Bladder cancer ; prognosis ; circadian rhythm ; anesthesia ; EZH2
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