Skip to content
2000
image of Global Trends in Hepatocellular Carcinoma and TGF-β Research: A Bibliometric and Visualization Analysis from 2000 to 2024

Abstract

Background

Transforming growth factor-beta (TGF-β) plays a pivotal role in advanced hepatocellular carcinoma (HCC) by modulating immune responses, inflammatory processes, and epithelial-mesenchymal transition (EMT) in hepatocytes. It has emerged as a key therapeutic target for HCC.

Objective

This study employs bibliometric analysis to examine literature published between 2000 and 2024, aiming to explore the critical roles of TGF-β in HCC and provide a theoretical foundation for future research.

Methods

This study utilized the Web of Science Core Collection (WoSCC) database to analyze publications from January 1, 2000, to October 16, 2024. Visualization tools such as CiteSpace, VOSviewer, and SCImago Graphica were utilized to assess publication trends, countries, institutions, journals, authors, keywords, and references, identifying hotspots, trends, and the evolution of TGF-β research in the context of HCC.

Results

The analysis encompassed 3,026 publications originating from 79 different countries. China was identified as the leading country in publication volume, with Fudan University being the most prolific institution. The journal Hepatology stood out as the leading publication in terms of both the volume of articles and citation influence. Keyword analysis revealed that recent research (2020–2024) has focused on metabolic regulation, the tumor immune microenvironment, and targeted therapies related to the TGF-β signaling pathway in HCC.

Conclusion

This study highlights the publication landscape, research trends, and hotspots of TGF-β-related HCC research from 2000 to 2024, providing valuable insights and a theoretical basis for future studies in this critical field.

© 2025 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037378714250529063227
2025-06-13
2025-09-26
Loading full text...

Full text loading...

/deliver/fulltext/cpps/10.2174/0113892037378714250529063227/BMS-CPPS-2024-179.html?itemId=/content/journals/cpps/10.2174/0113892037378714250529063227&mimeType=html&fmt=ahah

References

  1. Zheng Y. Wang S. Cai J. Ke A. Fan J. The progress of immune checkpoint therapy in primary liver cancer. Biochim. Biophys. Acta Rev. Cancer 2021 1876 2 188638 10.1016/j.bbcan.2021.188638 34688805
    [Google Scholar]
  2. Wang W. Wei C. Advances in the early diagnosis of hepatocellular carcinoma. Genes Dis. 2020 7 3 308 319 10.1016/j.gendis.2020.01.014 32884985
    [Google Scholar]
  3. Wang Y. Deng B. Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers. Cancer Metastasis Rev. 2023 42 3 629 652 10.1007/s10555‑023‑10084‑4 36729264
    [Google Scholar]
  4. Taniai M. Alcohol and hepatocarcinogenesis. Clin. Mol. Hepatol. 2020 26 4 736 741 10.3350/cmh.2020.0203 33053943
    [Google Scholar]
  5. Ceni E. Mello T. Galli A. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism. World J. Gastroenterol. 2014 20 47 17756 17772 10.3748/wjg.v20.i47.17756 25548474
    [Google Scholar]
  6. Fu Y. Maccioni L. Wang X.W. Greten T.F. Gao B. Alcohol-associated liver cancer. Hepatology 2024 80 6 1462 1479 10.1097/HEP.0000000000000890 38607725
    [Google Scholar]
  7. Yau T. Park J.W. Finn R.S. Cheng A.L. Mathurin P. Edeline J. Kudo M. Harding J.J. Merle P. Rosmorduc O. Wyrwicz L. Schott E. Choo S.P. Kelley R.K. Sieghart W. Assenat E. Zaucha R. Furuse J. Abou-Alfa G.K. El-Khoueiry A.B. Melero I. Begic D. Chen G. Neely J. Wisniewski T. Tschaika M. Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 23 1 77 90 10.1016/S1470‑2045(21)00604‑5 34914889
    [Google Scholar]
  8. Kudo M. Finn R.S. Qin S. Han K.H. Ikeda K. Piscaglia F. Baron A. Park J.W. Han G. Jassem J. Blanc J.F. Vogel A. Komov D. Evans T.R.J. Lopez C. Dutcus C. Guo M. Saito K. Kraljevic S. Tamai T. Ren M. Cheng A.L. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018 391 10126 1163 1173 10.1016/S0140‑6736(18)30207‑1 29433850
    [Google Scholar]
  9. Bruix J. Qin S. Merle P. Granito A. Huang Y.H. Bodoky G. Pracht M. Yokosuka O. Rosmorduc O. Breder V. Gerolami R. Masi G. Ross P.J. Song T. Bronowicki J.P. Ollivier-Hourmand I. Kudo M. Cheng A.L. Llovet J.M. Finn R.S. LeBerre M.A. Baumhauer A. Meinhardt G. Han G. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017 389 10064 56 66 10.1016/S0140‑6736(16)32453‑9 27932229
    [Google Scholar]
  10. Abou-Alfa G.K. Meyer T. Cheng A.L. El-Khoueiry A.B. Rimassa L. Ryoo B.Y. Cicin I. Merle P. Chen Y. Park J.W. Blanc J.F. Bolondi L. Klümpen H.J. Chan S.L. Zagonel V. Pressiani T. Ryu M.H. Venook A.P. Hessel C. Borgman-Hagey A.E. Schwab G. Kelley R.K. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N. Engl. J. Med. 2018 379 1 54 63 10.1056/NEJMoa1717002 29972759
    [Google Scholar]
  11. Zhu A.X. Kang Y.K. Yen C.J. Finn R.S. Galle P.R. Llovet J.M. Assenat E. Brandi G. Pracht M. Lim H.Y. Rau K.M. Motomura K. Ohno I. Merle P. Daniele B. Shin D.B. Gerken G. Borg C. Hiriart J.B. Okusaka T. Morimoto M. Hsu Y. Abada P.B. Kudo M. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 20 2 282 296 10.1016/S1470‑2045(18)30937‑9 30665869
    [Google Scholar]
  12. El-Khoueiry A.B. Sangro B. Yau T. Crocenzi T.S. Kudo M. Hsu C. Kim T.Y. Choo S.P. Trojan J. Welling T.H. Meyer T. Kang Y.K. Yeo W. Chopra A. Anderson J. dela Cruz C. Lang L. Neely J. Tang H. Dastani H.B. Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017 389 10088 2492 2502 10.1016/S0140‑6736(17)31046‑2 28434648
    [Google Scholar]
  13. Zhu A.X. Finn R.S. Edeline J. Cattan S. Ogasawara S. Palmer D. Verslype C. Zagonel V. Fartoux L. Vogel A. Sarker D. Verset G. Chan S.L. Knox J. Daniele B. Webber A.L. Ebbinghaus S.W. Ma J. Siegel A.B. Cheng A.L. Kudo M. Alistar A. Asselah J. Blanc J-F. Borbath I. Cannon T. Chung K. Cohn A. Cosgrove D.P. Damjanov N. Gupta M. Karino Y. Karwal M. Kaubisch A. Kelley R. Van Laethem J-L. Larson T. Lee J. Li D. Manhas A. Manji G.A. Numata K. Parsons B. Paulson A.S. Pinto C. Ramirez R. Ratnam S. Rizell M. Rosmorduc O. Sada Y. Sasaki Y. Stal P.I. Strasser S. Trojan J. Vaccaro G. Van Vlierberghe H. Weiss A. Weiss K-H. Yamashita T. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 19 7 940 952 10.1016/S1470‑2045(18)30351‑6 29875066
    [Google Scholar]
  14. Sangro B. Gomez-Martin C. de la Mata M. Iñarrairaegui M. Garralda E. Barrera P. Riezu-Boj J.I. Larrea E. Alfaro C. Sarobe P. Lasarte J.J. Pérez-Gracia J.L. Melero I. Prieto J. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J. Hepatol. 2013 59 1 81 88 10.1016/j.jhep.2013.02.022 23466307
    [Google Scholar]
  15. Huang A. Yang X.R. Chung W.Y. Dennison A.R. Zhou J. Targeted therapy for hepatocellular carcinoma. Signal Transduct. Target. Ther. 2020 5 1 146 10.1038/s41392‑020‑00264‑x 32782275
    [Google Scholar]
  16. Peng D. Fu M. Wang M. Wei Y. Wei X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol. Cancer 2022 21 1 104 10.1186/s12943‑022‑01569‑x 35461253
    [Google Scholar]
  17. Massagué J. Sheppard D. TGF-β signaling in health and disease. Cell 2023 186 19 4007 4037 10.1016/j.cell.2023.07.036 37714133
    [Google Scholar]
  18. Caja L. Sancho P. Bertran E. Fabregat I. Dissecting the effect of targeting the epidermal growth factor receptor on TGF-β-induced-apoptosis in human hepatocellular carcinoma cells. J. Hepatol. 2011 55 2 351 358 10.1016/j.jhep.2010.10.041 21147185
    [Google Scholar]
  19. Murillo M.M. Castillo G. Sánchez A. Fernández M. Fabregat I. Involvement of EGF receptor and c-Src in the survival signals induced by TGF-β1 in hepatocytes. Oncogene 2005 24 28 4580 4587 10.1038/sj.onc.1208664 15856020
    [Google Scholar]
  20. Giannelli G. Rani B. Dituri F. Cao Y. Palasciano G. Moving towards personalised therapy in patients with hepatocellular carcinoma: The role of the microenvironment. Gut 2014 63 10 1668 1676 10.1136/gutjnl‑2014‑307323 25053718
    [Google Scholar]
  21. Giannelli G. Koudelkova P. Dituri F. Mikulits W. Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J. Hepatol. 2016 65 4 798 808 10.1016/j.jhep.2016.05.007 27212245
    [Google Scholar]
  22. Franco D.L. Mainez J. Vega S. Sancho P. Murillo M.M. de Frutos C.A. del Castillo G. López-Blau C. Fabregat I. Nieto M.A. Snail1 suppresses TGF-β-induced apoptosis and is sufficient to trigger EMT in hepatocytes. J. Cell Sci. 2010 123 20 3467 3477 10.1242/jcs.068692 20930141
    [Google Scholar]
  23. Carmona-Cuenca I. Herrera B. Ventura J.J. Roncero C. Fernández M. Fabregat I. EGF blocks NADPH oxidase activation by TGF‐β in fetal rat hepatocytes, impairing oxidative stress, and cell death. J. Cell. Physiol. 2006 207 2 322 330 10.1002/jcp.20568 16331683
    [Google Scholar]
  24. Carmona-Cuenca I. Roncero C. Sancho P. Caja L. Fausto N. Fernández M. Fabregat I. Upregulation of the NADPH oxidase NOX4 by TGF-beta in hepatocytes is required for its pro-apoptotic activity. J. Hepatol. 2008 49 6 965 976 10.1016/j.jhep.2008.07.021 18845355
    [Google Scholar]
  25. Moreno-Càceres J. Mainez J. Mayoral R. Martín-Sanz P. Egea G. Fabregat I. Caveolin‐1‐dependent activation of the metalloprotease TACE/ADAM 17 by TGF ‐β in hepatocytes requires activation of Src and the NADPH oxidase NOX 1. FEBS J. 2016 283 7 1300 1310 10.1111/febs.13669 26815118
    [Google Scholar]
  26. Calon A. Tauriello D.V.F. Batlle E. TGF-beta in CAF-mediated tumor growth and metastasis. Semin. Cancer Biol. 2014 25 15 22 10.1016/j.semcancer.2013.12.008 24412104
    [Google Scholar]
  27. Zhang H-R. Wang X-D. Yang X. Chen D. Hao J. Cao R. Wu X-Z. An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells. Oncogene 2017 36 27 3831 3841 10.1038/onc.2016.512 28263980
    [Google Scholar]
  28. Malfettone A. Soukupova J. Bertran E. Crosas-Molist E. Lastra R. Fernando J. Koudelkova P. Rani B. Fabra Á. Serrano T. Ramos E. Mikulits W. Giannelli G. Fabregat I. Transforming growth factor-β-induced plasticity causes a migratory stemness phenotype in hepatocellular carcinoma. Cancer Lett. 2017 392 39 50 10.1016/j.canlet.2017.01.037 28161507
    [Google Scholar]
  29. Zhang M. Sui C. Dai B. Shen W. Lu J. Yang J. PEG10 is imperative for TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Oncol. Rep. 2017 37 1 510 518 10.3892/or.2016.5282 28004118
    [Google Scholar]
  30. Ninkov A. Frank J.R. Maggio L.A. Bibliometrics: Methods for studying academic publishing. Perspect. Med. Educ. 2021 11 3 173 176 10.1007/S40037‑021‑00695‑4 34914027
    [Google Scholar]
  31. Cooper I.D. Bibliometrics basics. J. Med. Libr. Assoc. 2015 103 4 217 218 10.3163/1536‑5050.103.4.013 26512226
    [Google Scholar]
  32. Chen C. Searching for intellectual turning points: Progressive knowledge domain visualization. Proc. Natl. Acad. Sci. USA 2004 101 Suppl. 1 5303 5310 10.1073/pnas.0307513100 14724295
    [Google Scholar]
  33. Gao X-L. Sui Y. Liu S. Sun Y-P. Knowledge domain and emerging trends in Alzheimer’s disease: A scientometric review based on CiteSpace analysis. Neural Regen. Res. 2019 14 9 1643 1650 10.4103/1673‑5374.255995 31089065
    [Google Scholar]
  34. Pei Z. Chen S. Ding L. Liu J. Cui X. Li F. Qiu F. Current perspectives and trend of nanomedicine in cancer: A review and bibliometric analysis. J. Control. Release 2022 352 211 241 10.1016/j.jconrel.2022.10.023 36270513
    [Google Scholar]
  35. Chen J. Gingold J.A. Su X. Immunomodulatory TGF-β signaling in hepatocellular carcinoma. Trends Mol. Med. 2019 25 11 1010 1023 10.1016/j.molmed.2019.06.007 31353124
    [Google Scholar]
  36. Shi X. Yang J. Deng S. Xu H. Wu D. Zeng Q. Wang S. Hu T. Wu F. Zhou H. TGF-β signaling in the tumor metabolic microenvironment and targeted therapies. J. Hematol. Oncol. 2022 15 1 135 10.1186/s13045‑022‑01349‑6 36115986
    [Google Scholar]
  37. Roehlen N. Crouchet E. Baumert T.F. Liver fibrosis: Mechanistic concepts and therapeutic perspectives. Cells 2020 9 4 875 10.3390/cells9040875 32260126
    [Google Scholar]
  38. Xing S. Yu W. Zhang X. Luo Y. Lei Z. Huang D. Lin J. Huang Y. Huang S. Nong F. Zhou C. Wei G. Isoviolanthin extracted from dendrobium officinale reverses TGF-β1-mediated epithelial–mesenchymal transition in hepatocellular carcinoma cells via deactivating the TGF-β/Smad and PI3K/Akt/mTOR signaling pathways. Int. J. Mol. Sci. 2018 19 6 1556 10.3390/ijms19061556 29882900
    [Google Scholar]
  39. Mancarella S. Cigliano A. Chieti A. Giannelli G. Dituri F. TGF-β as multifaceted orchestrator in HCC progression: Signaling, EMT, immune microenvironment, and novel therapeutic perspectives. Semin Liver Dis. 2019 39 1 053 069 10.1055/s‑0038‑1676121 30586675
    [Google Scholar]
  40. Dimitroulis D. Damaskos C. Valsami S. Davakis S. Garmpis N. Spartalis E. Athanasiou A. Moris D. Sakellariou S. Kykalos S. Tsourouflis G. Garmpi A. Delladetsima I. Kontzoglou K. Kouraklis G. From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world. World J. Gastroenterol. 2017 23 29 5282 5294 10.3748/wjg.v23.i29.5282 28839428
    [Google Scholar]
  41. Xie D.Y. Ren Z.G. Zhou J. Fan J. Gao Q. 2019 Chinese clinical guidelines for the management of hepatocellular carcinoma: Updates and insights. Hepatobiliary Surg. Nutr. 2020 9 4 452 463 10.21037/hbsn‑20‑480 32832496
    [Google Scholar]
  42. Xin X. Cheng X. Zeng F. Xu Q. Hou L. The role of TGF-β/SMAD signaling in hepatocellular carcinoma: From mechanism to therapy and prognosis. Int. J. Biol. Sci. 2024 20 4 1436 1451 10.7150/ijbs.89568 38385079
    [Google Scholar]
  43. Lei Y. Tang R. Xu J. Wang W. Zhang B. Liu J. Yu X. Shi S. Applications of single-cell sequencing in cancer research: Progress and perspectives. J. Hematol. Oncol. 2021 14 1 91 10.1186/s13045‑021‑01105‑2 34108022
    [Google Scholar]
  44. Li P.H. Kong X.Y. He Y.Z. Liu Y. Peng X. Li Z.H. Xu H. Luo H. Park J. Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy. Mil. Med. Res. 2022 9 1 52 10.1186/s40779‑022‑00414‑y 36154923
    [Google Scholar]
  45. Song M. He J. Pan Q.Z. Yang J. Zhao J. Zhang Y.J. Huang Y. Tang Y. Wang Q. He J. Gu J. Li Y. Chen S. Zeng J. Zhou Z.Q. Yang C. Han Y. Chen H. Xiang T. Weng D.S. Xia J.C. Cancer-associated fibroblast-mediated cellular crosstalk supports hepatocellular carcinoma progression. Hepatology 2021 73 5 1717 1735 10.1002/hep.31792 33682185
    [Google Scholar]
  46. Gu J. Zhou J. Chen Q. Xu X. Gao J. Li X. Shao Q. Zhou B. Zhou H. Wei S. Wang Q. Liang Y. Lu L. Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Rep. 2022 39 12 110986 10.1016/j.celrep.2022.110986 35732125
    [Google Scholar]
  47. O’Rourke J.M. Sagar V.M. Shah T. Shetty S. Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer. World J. Gastroenterol. 2018 24 39 4436 4447 10.3748/wjg.v24.i39.4436 30357021
    [Google Scholar]
  48. Affo S. Yu L.X. Schwabe R.F. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu. Rev. Pathol. 2017 12 1 153 186 10.1146/annurev‑pathol‑052016‑100322 27959632
    [Google Scholar]
  49. Baglieri J. Brenner D.A. Kisseleva T. The role of fibrosis and liver-associated fibroblasts in the pathogenesis of hepatocellular carcinoma. Int. J. Mol. Sci. 2019 20 7 1723 10.3390/ijms20071723 30959975
    [Google Scholar]
  50. Mederacke I. Hsu C.C. Troeger J.S. Huebener P. Mu X. Dapito D.H. Pradere J.P. Schwabe R.F. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat. Commun. 2013 4 1 2823 10.1038/ncomms3823 24264436
    [Google Scholar]
  51. Henderson N.C. Arnold T.D. Katamura Y. Giacomini M.M. Rodriguez J.D. McCarty J.H. Pellicoro A. Raschperger E. Betsholtz C. Ruminski P.G. Griggs D.W. Prinsen M.J. Maher J.J. Iredale J.P. Lacy-Hulbert A. Adams R.H. Sheppard D. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat. Med. 2013 19 12 1617 1624 10.1038/nm.3282 24216753
    [Google Scholar]
  52. Puche J.E. Lee Y.A. Jiao J. Aloman C. Fiel M.I. Muñoz U. Kraus T. Lee T. Yee H.F. Friedman S.L. A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice. Hepatology 2013 57 1 339 350 10.1002/hep.26053 22961591
    [Google Scholar]
  53. Lua I. Li Y. Zagory J.A. Wang K.S. French S.W. Sévigny J. Asahina K. Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers. J. Hepatol. 2016 64 5 1137 1146 10.1016/j.jhep.2016.01.010 26806818
    [Google Scholar]
  54. Li Y. Wang J. Asahina K. Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial–mesenchymal transition in liver injury. Proc. Natl. Acad. Sci. USA 2013 110 6 2324 2329 10.1073/pnas.1214136110 23345421
    [Google Scholar]
  55. Fausther M. Goree J.R. Lavoie É.G. Graham A.L. Sévigny J. Dranoff J.A. Establishment and characterization of rat portal myofibroblast cell lines. PLoS One 2015 10 3 e0121161 10.1371/journal.pone.0121161 25822334
    [Google Scholar]
  56. Inui N. Sakai S. Kitagawa M. Molecular pathogenesis of pulmonary fibrosis, with focus on pathways related to TGF-β and the ubiquitin-proteasome pathway. Int. J. Mol. Sci. 2021 22 11 6107 10.3390/ijms22116107 34198949
    [Google Scholar]
  57. Koyama Y. Wang P. Liang S. Iwaisako K. Liu X. Xu J. Zhang M. Sun M. Cong M. Karin D. Taura K. Benner C. Heinz S. Bera T. Brenner D.A. Kisseleva T. Mesothelin/mucin 16 signaling in activated portal fibroblasts regulates cholestatic liver fibrosis. J. Clin. Invest. 2017 127 4 1254 1270 10.1172/JCI88845 28287406
    [Google Scholar]
  58. Prockop D.J. Inflammation, fibrosis, and modulation of the process by mesenchymal stem/stromal cells. Matrix Biol. 2016 51 7 13 10.1016/j.matbio.2016.01.010 26807758
    [Google Scholar]
  59. Hao Y. Baker D. ten Dijke P. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci. 2019 20 11 2767 10.3390/ijms20112767 31195692
    [Google Scholar]
  60. Jolly M.K. Ware K.E. Gilja S. Somarelli J.A. Levine H. EMT and MET: Necessary or permissive for metastasis? Mol. Oncol. 2017 11 7 755 769 10.1002/1878‑0261.12083 28548345
    [Google Scholar]
  61. Zheng X. Carstens J.L. Kim J. Scheible M. Kaye J. Sugimoto H. Wu C.C. LeBleu V.S. Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015 527 7579 525 530 10.1038/nature16064 26560028
    [Google Scholar]
  62. Li W. Kang Y. Probing the fifty shades of EMT in metastasis. Trends Cancer 2016 2 2 65 67 10.1016/j.trecan.2016.01.001 27042694
    [Google Scholar]
  63. Nikitorowicz-Buniak J. Denton C.P. Abraham D. Stratton R. Partially evoked epithelial-mesenchymal transition (EMT) is associated with increased TGFβ signaling within lesional scleroderma skin. PLoS One 2015 10 7 e0134092 10.1371/journal.pone.0134092 26217927
    [Google Scholar]
  64. Buitrago-Molina L.E. Marhenke S. Becker D. Geffers R. Itzel T. Teufel A. Jaeschke H. Lechel A. Unger K. Markovic J. Sharma A.D. Marquardt J.U. Saborowski M. Saborowski A. Vogel A. p53-independent induction of p21 fails to control regeneration and hepatocarcinogenesis in a murine liver injury model. Cell. Mol. Gastroenterol. Hepatol. 2021 11 5 1387 1404 10.1016/j.jcmgh.2021.01.006 33484913
    [Google Scholar]
  65. Michalski M. Bauer M. Walz F. Tümen D. Heumann P. Stöckert P. Gunckel M. Kunst C. Kandulski A. Schmid S. Müller M. Gülow K. Simultaneous inhibition of Mcl-1 and Bcl-2 induces synergistic cell death in hepatocellular carcinoma. Biomedicines 2023 11 6 1666 10.3390/biomedicines11061666 37371761
    [Google Scholar]
  66. Li Y. Xiong H. Correlation of LAGE3 with unfavorable prognosis and promoting tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways. BMC Cancer 2022 22 1 298 10.1186/s12885‑022‑09398‑3 35313850
    [Google Scholar]
  67. Yan X. Wu J. Jiang Q. Cheng H. Han J.D.J. Chen Y.G. CXXC5 suppresses hepatocellular carcinoma by promoting TGF-β-induced cell cycle arrest and apoptosis. J. Mol. Cell Biol. 2018 10 1 48 59 10.1093/jmcb/mjx042 29036306
    [Google Scholar]
  68. Zhang Y. Alexander P.B. Wang X.F. TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harb. Perspect. Biol. 2017 9 4 a022145 10.1101/cshperspect.a022145 27920038
    [Google Scholar]
  69. Yang J.H. Kim N.H. Yun J.S. Cho E.S. Cha Y.H. Cho S.B. Lee S.H. Cha S.Y. Kim S.Y. Choi J. Nguyen T.T.M. Park S. Kim H.S. Yook J.I. Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression. Life Sci. Alliance 2020 3 7 e202000683 10.26508/lsa.202000683 32487689
    [Google Scholar]
  70. Soukupova J. Malfettone A. Bertran E. Hernández-Alvarez M.I. Peñuelas-Haro I. Dituri F. Giannelli G. Zorzano A. Fabregat I. Epithelial–mesenchymal transition (EMT) induced by TGF-β in hepatocellular carcinoma cells reprograms lipid metabolism. Int. J. Mol. Sci. 2021 22 11 5543 10.3390/ijms22115543 34073989
    [Google Scholar]
  71. Du D. Liu C. Qin M. Zhang X. Xi T. Yuan S. Hao H. Xiong J. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. Acta Pharm. Sin. B 2022 12 2 558 580 10.1016/j.apsb.2021.09.019 35256934
    [Google Scholar]
  72. Wang H. Liu F. Wu X. Zhu G. Tang Z. Qu W. Zhao Q. Huang R. Tian M. Fang Y. Jiang X. Tao C. Gao J. Liu W. Zhou J. Fan J. Wu D. Shi Y. Cancer-associated fibroblasts contributed to hepatocellular carcinoma recurrence and metastasis via CD36-mediated fatty-acid metabolic reprogramming. Exp. Cell Res. 2024 435 2 113947 10.1016/j.yexcr.2024.113947 38301989
    [Google Scholar]
  73. Gjorgjieva M. Calderaro J. Monteillet L. Silva M. Raffin M. Brevet M. Romestaing C. Roussel D. Zucman-Rossi J. Mithieux G. Rajas F. Dietary exacerbation of metabolic stress leads to accelerated hepatic carcinogenesis in glycogen storage disease type Ia. J. Hepatol. 2018 69 5 1074 1087 10.1016/j.jhep.2018.07.017 30193922
    [Google Scholar]
  74. Sangro B. Sarobe P. Hervás-Stubbs S. Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 2021 18 8 525 543 10.1038/s41575‑021‑00438‑0 33850328
    [Google Scholar]
  75. Flecken T. Schmidt N. Hild S. Gostick E. Drognitz O. Zeiser R. Schemmer P. Bruns H. Eiermann T. Price D.A. Blum H.E. Neumann-Haefelin C. Thimme R. Immunodominance and functional alterations of tumor-associated antigen-specific CD8+ T-cell responses in hepatocellular carcinoma. Hepatology 2014 59 4 1415 1426 10.1002/hep.26731 24002931
    [Google Scholar]
  76. Xiao Z. Ji Q. Fu Y. Gao S. Hu Y. Liu W. Chen G. Mu Y. Chen J. Liu P. Amygdalin ameliorates liver fibrosis through inhibiting activation of TGF-β/Smad signaling. Chin. J. Integr. Med. 2023 29 4 316 324 10.1007/s11655‑021‑3304‑y 34816365
    [Google Scholar]
  77. Wang B. Bai W. Ma H. Li F. Regulatory effect of PD1/PD-ligand 1 (PD-L1) on treg cells in patients with idiopathic pulmonary fibrosis. Med. Sci. Monit. 2021 26 e927577 10.12659/MSM.927577 33386384
    [Google Scholar]
  78. Zhulai G. Oleinik E. Targeting regulatory T cells in anti‐PD‐1/PD‐L1 cancer immunotherapy. Scand. J. Immunol. 2022 95 3 e13129 10.1111/sji.13129 34936125
    [Google Scholar]
  79. Sengez B. Carr B.I. Alotaibi H. EMT and inflammation: Crossroads in HCC. J. Gastrointest. Cancer 2023 54 1 204 212 10.1007/s12029‑021‑00801‑z 35020133
    [Google Scholar]
  80. Liu S.J. Dang H.X. Lim D.A. Feng F.Y. Maher C.A. Long noncoding RNAs in cancer metastasis. Nat. Rev. Cancer 2021 21 7 446 460 10.1038/s41568‑021‑00353‑1 33953369
    [Google Scholar]
  81. Aruga N. Kijima H. Masuda R. Onozawa H. Yoshizawa T. Tanaka M. Inokuchi S. Iwazaki M. Epithelial-mesenchymal transition (EMT) is correlated with patient’s prognosis of lung squamous cell carcinoma. Tokai J. Exp. Clin. Med. 2018 43 1 5 13 29637533
    [Google Scholar]
  82. Deshmukh A.P. Vasaikar S.V. Tomczak K. Tripathi S. den Hollander P. Arslan E. Chakraborty P. Soundararajan R. Jolly M.K. Rai K. Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing. Proc. Natl. Acad. Sci. USA 2021 118 19 e2102050118 10.1073/pnas.2102050118 33941680
    [Google Scholar]
  83. Rumgay H. Shield K. Charvat H. Ferrari P. Sornpaisarn B. Obot I. Islami F. Lemmens V.E.P.P. Rehm J. Soerjomataram I. Global burden of cancer in 2020 attributable to alcohol consumption: A population-based study. Lancet Oncol. 2021 22 8 1071 1080 10.1016/S1470‑2045(21)00279‑5 34270924
    [Google Scholar]
  84. Choudhary H.B. Mandlik S.K. Mandlik D.S. Role of p53 suppression in the pathogenesis of hepatocellular carcinoma. World J. Gastrointest. Pathophysiol. 2023 14 3 46 70 10.4291/wjgp.v14.i3.46 37304923
    [Google Scholar]
  85. Liu S.Y. Tsai I.T. Hsu Y.C. Alcohol-related liver disease: Basic Mechanisms and clinical perspectives. Int. J. Mol. Sci. 2021 22 10 5170 10.3390/ijms22105170 34068269
    [Google Scholar]
  86. Kim H.G. Cho J. Kim J. Kim S.J. The role of epigenetic changes in the progression of alcoholic steatohepatitis. Front. Physiol. 2021 12 691738 10.3389/fphys.2021.691738 34335299
    [Google Scholar]
  87. Hussain Y. Singh J. Raza W. Meena A. Rajak S. Sinha R.A. Luqman S. Purpurin ameliorates alcohol-induced hepatotoxicity by reducing ROS generation and promoting Nrf2 expression. Life Sci. 2022 309 120964 10.1016/j.lfs.2022.120964 36115584
    [Google Scholar]
  88. Haag F. Janicova A. Xu B. Powerski M. Fachet M. Bundkirchen K. Neunaber C. Marzi I. Relja B. Sturm R. Reduced phagocytosis, ROS production and enhanced apoptosis of leukocytes upon alcohol drinking in healthy volunteers. Eur. J. Trauma Emerg. Surg. 2022 48 4 2689 2699 10.1007/s00068‑021‑01643‑x 33783566
    [Google Scholar]
  89. Kumar S. Singla B. Singh A.K. Thomas-Gooch S.M. Zhi K. Singh U.P. Hepatic, extrahepatic and extracellular vesicle cytochrome P450 2E1 in alcohol and acetaminophen-mediated adverse interactions and potential treatment options. Cells 2022 11 17 2620 10.3390/cells11172620 36078027
    [Google Scholar]
  90. Le Daré B. Lagente V. Gicquel T. Ethanol and its metabolites: Update on toxicity, benefits, and focus on immunomodulatory effects. Drug Metab. Rev. 2019 51 4 545 561 10.1080/03602532.2019.1679169 31646907
    [Google Scholar]
  91. Kim H.G. Huang M. Xin Y. Zhang Y. Zhang X. Wang G. Liu S. Wan J. Ahmadi A.R. Sun Z. Liangpunsakul S. Xiong X. Dong X.C. The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice. J. Hepatol. 2019 71 5 960 969 10.1016/j.jhep.2019.06.019 31295533
    [Google Scholar]
  92. Xue Y. Li X. Tian Y. Huang X. Zhang L. Li J. Hou H. Dong P. Wang J. Salmon sperm DNA prevents acute liver injury by regulating alcohol‐induced steatosis and restores chronic hepatosis via alleviating inflammation and apoptosis. J. Food Biochem. 2022 46 10 e14346 10.1111/jfbc.14346 35933684
    [Google Scholar]
  93. Hao X. Zheng Z. Liu H. Zhang Y. Kang J. Kong X. Rong D. Sun G. Sun G. Liu L. Yu H. Tang W. Wang X. Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing. Redox Biol. 2022 56 102463 10.1016/j.redox.2022.102463 36108528
    [Google Scholar]
  94. Chi H. Zhao S. Yang J. Gao X. Peng G. Zhang J. Xie X. Song G. Xu K. Xia Z. Chen S. Zhao J. T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing. Front. Immunol. 2023 14 1137025 10.3389/fimmu.2023.1137025 37006257
    [Google Scholar]
  95. Brunner S.F. Roberts N.D. Wylie L.A. Moore L. Aitken S.J. Davies S.E. Sanders M.A. Ellis P. Alder C. Hooks Y. Abascal F. Stratton M.R. Martincorena I. Hoare M. Campbell P.J. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 2019 574 7779 538 542 10.1038/s41586‑019‑1670‑9 31645727
    [Google Scholar]
  96. Wang P. Gao X. Liang M. Fang Y. Jia J. Tian J. Li Z. Qin X. Dose-effect/toxicity of bupleuri radix on chronic unpredictable mild stress and normal rats based on liver metabolomics. Front. Pharmacol. 2021 12 627451 10.3389/fphar.2021.627451 34557088
    [Google Scholar]
/content/journals/cpps/10.2174/0113892037378714250529063227
Loading
/content/journals/cpps/10.2174/0113892037378714250529063227
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keywords: Hepatocellular carcinoma ; visualization ; hotspots ; bibliometrics ; TGF-β
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test