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2000
Volume 32, Issue 19
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X
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Abstract

Background

Vasculogenic mimicry, a novel neovascularization pattern of aggressive tumors, is associated with poor clinical outcomes.

Objective

The aim of this research was to establish a new model, termed VC score, to predict the prognosis, Tumor Microenvironment (TME) components, and immunotherapeutic response in Hepatocellular Carcinoma (HCC).

Methods

The expression data of the public databases were used to develop the prognostic model. Consensus clustering was performed to confirm the molecular subtypes with ideal clustering efficacy. The high- and low-risk groups were stratified utilizing the VC score. Various methodologies, including survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Dysfunction and Exclusion scores (TIDE), Immunophenoscore (IPS), and nomogram, were utilized for verification of the model performance and to characterize the immune status of HCC tissues. GSEA was performed to mine functional pathway information.

Results

The survival and immune characteristics varied between the three molecular subtypes. A five-gene signature (TPX2, CDC20, CFHR4, SPP1, and NQO1) was verified to function as an independent predictive factor for the prognosis of patients with HCC. The high-risk group exhibited lower Overall Survival (OS) rates and higher mortality rates in comparison to the low-risk group. Patients in the low-risk group were predicted to benefit from immune checkpoint inhibitor therapy and exhibit increased sensitivity to immunotherapy. Enrichment analysis revealed that signaling pathways linked to the cell cycle and DNA replication processes exhibited enrichment in the high-risk group.

Conclusion

The VC score holds the potential to establish individualized treatment plans and clinical management strategies for patients with HCC.

© 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
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2025-10-11

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References

  1. RumgayH. ArnoldM. FerlayJ. LesiO. CabasagC.J. VignatJ. LaversanneM. McGlynnK.A. SoerjomataramI. Global burden of primary liver cancer in 2020 and predictions to 2040.J. Hepatol.20227761598160610.1016/j.jhep.2022.08.02136208844
     [Google Scholar]
  2. WangY. WangJ. LiX. XiongX. WangJ. ZhouZ. ZhuX. GuY. DominissiniD. HeL. TianY. YiC. FanZ. N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism.Nat. Commun.2021121631410.1038/s41467‑021‑26718‑634728628
     [Google Scholar]
  3. VogelA. MeyerT. SapisochinG. SalemR. SaborowskiA. Hepatocellular carcinoma.Lancet2022400103601345136210.1016/S0140‑6736(22)01200‑436084663
     [Google Scholar]
  4. LlovetJ.M. KelleyR.K. VillanuevaA. SingalA.G. PikarskyE. RoayaieS. LencioniR. KoikeK. Zucman-RossiJ. FinnR.S. Hepatocellular carcinoma.Nat. Rev. Dis. Primers202171610.1038/s41572‑020‑00240‑333479224
     [Google Scholar]
  5. DonneR. LujambioA. The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma.Hepatology20237751773179610.1002/hep.3274035989535
     [Google Scholar]
  6. TakiM. AbikoK. UkitaM. MurakamiR. YamanoiK. YamaguchiK. HamanishiJ. BabaT. MatsumuraN. MandaiM. Tumor immune microenvironment during epithelial-mesenchymal transition.Clin. Cancer Res.202127174669467910.1158/1078‑0432.CCR‑20‑445933827891
     [Google Scholar]
  7. WeiX. ChenY. JiangX. PengM. LiuY. MoY. RenD. HuaY. YuB. ZhouY. LiaoQ. WangH. XiangB. ZhouM. LiX. LiG. LiY. XiongW. ZengZ. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.Mol. Cancer2021201710.1186/s12943‑020‑01288‑133397409
     [Google Scholar]
  8. Herrera-VargasA.K. García-RodríguezE. Olea-FloresM. Mendoza-CatalánM.A. Flores-AlfaroE. Navarro-TitoN. Pro-angiogenic activity and vasculogenic mimicry in the tumor microenvironment by leptin in cancer.Cytokine Growth Factor Rev.202162234110.1016/j.cytogfr.2021.10.00634736827
     [Google Scholar]
  9. LuoQ. WangJ. ZhaoW. PengZ. LiuX. LiB. ZhangH. ShanB. ZhangC. DuanC. Vasculogenic mimicry in carcinogenesis and clinical applications.J. Hematol. Oncol.20201311910.1186/s13045‑020‑00858‑632169087
     [Google Scholar]
  10. QiaoK. LiuY. XuZ. ZhangH. ZhangH. ZhangC. ChangZ. LuX. LiZ. LuoC. LiuY. YangC. SunT. RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway.Angiogenesis2021241839610.1007/s10456‑020‑09744‑832920668
     [Google Scholar]
  11. ManiotisA.J. FolbergR. HessA. SeftorE.A. GardnerL.M.G. Pe’erJ. TrentJ.M. MeltzerP.S. HendrixM.J.C. Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry.Am. J. Pathol.1999155373975210.1016/S0002‑9440(10)65173‑510487832
     [Google Scholar]
  12. OuH. ChenZ. XiangL. FangY. XuY. LiuQ. HuZ. LiX. HuangY. YangD. Frizzled 2-induced epithelial-mesenchymal transition correlates with vasculogenic mimicry, stemness, and Hippo signaling in hepatocellular carcinoma.Cancer Sci.201911041169118210.1111/cas.1394930677195
     [Google Scholar]
  13. ShiY. ShangJ. LiY. ZhongD. ZhangZ. YangQ. LaiC. FengT. YaoY. HuangX. ITGA5 and ITGB1 contribute to Sorafenib resistance by promoting vasculogenic mimicry formation in hepatocellular carcinoma.Cancer Med.20231233786379610.1002/cam4.511035946175
     [Google Scholar]
  14. SunB. ZhangS. ZhangD. DuJ. GuoH. ZhaoX. ZhangW. HaoX. Vasculogenic mimicry is associated with high tumor grade, invasion and metastasis, and short survival in patients with hepatocellular carcinoma.Oncol. Rep.200616469369810.3892/or.16.4.69316969481
     [Google Scholar]
  15. ZhengN. ZhangS. WuW. ZhangN. WangJ. Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma.Pharmacol. Res.202116610550710.1016/j.phrs.2021.10550733610718
     [Google Scholar]
  16. ZhangC. XiaoJ. YuanT. HeY. DengD. XiaoZ. ChenJ. ZuX. LiuP. LiuZ. Molecular vasculogenic mimicry–related signatures predict clinical outcomes and therapeutic responses in bladder cancer: Results from real- world cohorts.Front. Pharmacol.202314116311510.3389/fphar.2023.116311537197406
     [Google Scholar]
  17. FriedmanJ. HastieT. TibshiraniR. Regularization paths for generalized linear models via coordinate descent.J. Stat. Softw.201033112210.18637/jss.v033.i0120808728
     [Google Scholar]
  18. CharoentongP. FinotelloF. AngelovaM. MayerC. EfremovaM. RiederD. HacklH. TrajanoskiZ. Pan- cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade.Cell Rep.201718124826210.1016/j.celrep.2016.12.01928052254
     [Google Scholar]
  19. BindeaG. MlecnikB. TosoliniM. KirilovskyA. WaldnerM. ObenaufA.C. AngellH. FredriksenT. LafontaineL. BergerA. BrunevalP. FridmanW.H. BeckerC. PagèsF. SpeicherM.R. TrajanoskiZ. GalonJ. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.Immunity201339478279510.1016/j.immuni.2013.10.00324138885
     [Google Scholar]
  20. HeY. JiangZ. ChenC. WangX. Classification of triple-negative breast cancers based on immunogenomic profiling.J. Exper. Clin. Cancer Res.201837327
     [Google Scholar]
  21. LuY. WangW. LiuZ. MaJ. ZhouX. FuW. Long non-coding RNA profile study identifies a metabolism-related signature for colorectal cancer.Mol. Med.20212718310.1186/s10020‑021‑00343‑x34344319
     [Google Scholar]
  22. YoshiharaK. ShahmoradgoliM. MartínezE. VegesnaR. KimH. Torres-GarciaW. TreviñoV. ShenH. LairdP.W. LevineD.A. CarterS.L. GetzG. Stemke-HaleK. MillsG.B. VerhaakR.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data.Nat. Commun.201341261210.1038/ncomms361224113773
     [Google Scholar]
  23. ZhaoS. WangL. DingW. YeB. ChengC. ShaoJ. LiuJ. ZhouH. Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework.Front. Endocrinol.202314118040410.3389/fendo.2023.118040437152941
     [Google Scholar]
  24. García-MuleroS. AlonsoM.H. PardoJ. SantosC. SanjuanX. SalazarR. MorenoV. PiulatsJ.M. Sanz- PamplonaR. Lung metastases share common immune features regardless of primary tumor origin.J. Immunother. Cancer202081e00049110.1136/jitc‑2019‑00049132591432
     [Google Scholar]
  25. WuT. HuE. XuS. ChenM. GuoP. DaiZ. FengT. ZhouL. TangW. ZhanL. FuX. LiuS. BoX. YuG. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.Innovation20212310014110.1016/j.xinn.2021.10014134557778
     [Google Scholar]
  26. ShenX. ZhaoB. Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis.BMJ2018362k352910.1136/bmj.k352930201790
     [Google Scholar]
  27. Aguirre-PortolésC. BirdA.W. HymanA. CañameroM. Pérez de CastroI. MalumbresM. Tpx2 controls spindle integrity, genome stability, and tumor development.Cancer Res.20127261518152810.1158/0008‑5472.CAN‑11‑197122266221
     [Google Scholar]
  28. BillR. WirapatiP. MessemakerM. RohW. ZittiB. DuvalF. KissM. ParkJ.C. SaalT.M. HoelzlJ. TarussioD. BenedettiF. TissotS. KandalaftL. VarroneM. CirielloG. McKeeT.A. MonnierY. MermodM. BlaumE.M. GushterovaI. GonyeA.L.K. HacohenN. GetzG. MempelT.R. KleinA.M. WeisslederR. FaquinW.C. SadowP.M. LinD. PaiS.I. Sade-FeldmanM. PittetM.J. CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers.Science2023381665751552410.1126/science.ade229237535729
     [Google Scholar]
  29. LiuY. XunZ. MaK. LiangS. LiX. ZhouS. SunL. LiuY. DuY. GuoX. CuiT. ZhouH. WangJ. YinD. SongR. ZhangS. CaiW. MengF. GuoH. ZhangB. YangD. BaoR. HuQ. WangJ. YeY. LiuL. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy.J. Hepatol.202378477078210.1016/j.jhep.2023.01.01136708811
     [Google Scholar]
  30. CulbertsonB. GarciaK. MarkettD. AsgharianH. ChenL. FishL. NavickasA. YuJ. WooB. NandaA.S. ChoiB. ZhouS. RabinowitzJ. GoodarziH. A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression.Nat. Can.20234568269810.1038/s43018‑023‑00554‑737169843
     [Google Scholar]
  31. SingalA.G. KanwalF. LlovetJ.M. Global trends in hepatocellular carcinoma epidemiology: Implications for screening, prevention and therapy.Nat. Rev. Clin. Oncol.2023201286488410.1038/s41571‑023‑00825‑337884736
     [Google Scholar]
  32. LlovetJ.M. De BaereT. KulikL. HaberP.K. GretenT.F. MeyerT. LencioniR. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.Nat. Rev. Gastroenterol. Hepatol.202118529331310.1038/s41575‑020‑00395‑033510460
     [Google Scholar]
  33. HuangX.Y. HuangZ.L. HuangJ. XuB. HuangX.Y. XuY.H. ZhouJ. TangZ.Y. Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis.J. Exp. Clin. Cancer Res.20203912010.1186/s13046‑020‑1529‑931973767
     [Google Scholar]
  34. SunT. SunB. ZhaoX. ZhaoN. DongX. CheN. YaoZ. MaY. GuQ. ZongW. LiuZ. Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: A study of hepatocellular carcinoma.Hepatology20115451690170610.1002/hep.2454321748764
     [Google Scholar]
  35. WangM. ZhaoX. ZhuD. LiuT. LiangX. LiuF. ZhangY. DongX. SunB. HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment.J. Exp. Clin. Cancer Res.20173616010.1186/s13046‑017‑0533‑128449718
     [Google Scholar]
  36. ChuZ. ShiX. ChenG. HeX. QianY. WangH. TaoL. LiuY. JiangW. ChenJ. COE inhibits vasculogenic mimicry by targeting EphA2 in hepatocellular carcinoma, a research based on proteomics analysis.Front. Pharmacol.20211261973210.3389/fphar.2021.61973233867982
     [Google Scholar]
  37. ShuaiQ. CaoL. QinZ. ZhangY. GuZ. YangJ. VE-cadherin fusion protein substrate enhanced the vasculogenic mimicry capability of hepatocellular carcinoma cells.J. Mater. Chem. B Mater. Biol. Med.2020881699171210.1039/C9TB02790D32016269
     [Google Scholar]
  38. XiaoT. ZhangQ. ZongS. ZhongW. QinY. BiZ. ChenS. LiuH. WeiJ. ZhouB. WangL. ZhouH. LiuY. SunT. YangC. Protease-activated receptor-1 (PAR1) promotes epithelial-endothelial transition through Twist1 in hepatocellular carcinoma.J. Exp. Clin. Cancer Res.201837118510.1186/s13046‑018‑0858‑430081924
     [Google Scholar]
  39. LiuB. CaoJ. WuB. HaoK. WangX. ChenX. ShenZ. METTL3 and STAT3 form a positive feedback loop to promote cell metastasis in hepatocellular carcinoma.Cell Commun. Signal.202321112110.1186/s12964‑023‑01148‑737231451
     [Google Scholar]
  40. HeH. ChenS. FanZ. DongY. WangY. LiS. SunX. SongY. YangJ. CaoQ. JiangJ. WangX. WenW. WangH. Multi-dimensional single-cell characterization revealed suppressive immune microenvironment in AFP-positive hepatocellular carcinoma.Cell Discov.2023916010.1038/s41421‑023‑00563‑x37336873
     [Google Scholar]
  41. PengJ.Y. CaiD.K. ZengR.L. ZhangC.Y. LiG.C. ChenS.F. YuanX.Q. PengL. Upregulation of superenhancer-driven LncRNA FASRL by USF1 promotes de novo fatty acid biosynthesis to exacerbate hepatocellular carcinoma.Adv. Sci.2023101220471110.1002/advs.20220471136307901
     [Google Scholar]
  42. CaoH. ChuX. WangZ. GuoC. ShaoS. XiaoJ. ZhengJ. ZhangD. High FOXK1 expression correlates with poor outcomes in hepatocellular carcinoma and regulates stemness of hepatocellular carcinoma cells.Life Sci.201922812813410.1016/j.lfs.2019.04.06831054270
     [Google Scholar]
  43. WangF. ZhaoW. GaoY. ZhouJ. LiH. ZhangG. GuoD. XieC. LiJ. YinZ. ZhangJ. CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis.J. exper. clin. canc. res.201938286
     [Google Scholar]
  44. YuH. WangC. KeS. BaiM. XuY. LuS. FengZ. QianB. XuY. ZhouM. LiZ. YinB. LiX. HuaY. ZhouY. PanS. FuY. MaY. Identification of CFHR4 as a potential prognosis biomarker associated with lmmune infiltrates in hepatocellular carcinoma.Front. Immunol.20221389275010.3389/fimmu.2022.89275035812416
     [Google Scholar]
  45. ZhaoW. JiangL. FangT. FangF. LiuY. ZhaoY. YouY. ZhouH. SuX. WangJ. LiuS. ChenY. WanJ. HuangX. β-lapachone selectively kills hepatocellular carcinoma cells by targeting NQO1 to induce extensive DNA damage and PARP1 hyperactivation.Front. Oncol.20211174728210.3389/fonc.2021.74728234676172
     [Google Scholar]
  46. WangX. LiuY. HanA. TangC. XuR. FengL. YangY. ChenL. LinZ. The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability.Oncogene202241475107512010.1038/s41388‑022‑02477‑636253445
     [Google Scholar]
  47. ShiM. DaiW.Q. JiaR.R. ZhangQ.H. WeiJ. WangY.G. XiangS.H. LiuB. XuL. APCCDC20-mediated degradation of PHD3 stabilizes HIF-1a and promotes tumorigenesis in hepatocellular carcinoma.Cancer Lett.202149614415510.1016/j.canlet.2020.10.01133039559
     [Google Scholar]
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Clinical Significance of a Novel Vasculogenic Mimicry-based Prognostic Model in Hepatocellular Carcinoma
Curr. Med. Chem. 32, 3926 (2025); https://doi.org/10.2174/0109298673298862240510073543
/content/journals/cmc/10.2174/0109298673298862240510073543
/content/journals/cmc/10.2174/0109298673298862240510073543
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  • Article Type:     Research Article
Keyword(s): Hepatocellular carcinoma; immunotherapy; machine learning; prognostic prediction model; tumor microenvironment; vasculogenic mimicry

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