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2000
Volume 14, Issue 2
  • ISSN: 2211-5501
  • E-ISSN: 2211-551X

Abstract

Introduction

Pancreatic cancer is the sixth leading cause of death with a limited validated biomarker. Finding and validating diagnostic/prognostic markers can be improved by combining both forms of data in a multi-omics approach, which can offer a more comprehensive outcome.

Methods

GEO datasets were utilized to identify differentially expressed aquaporins in pancreatic cancer and validated through TCGA-PAAD data. Protein Data Commons (PDC) was used to analyse differentially expressed proteins in PAAD. Functional enrichment analysis and immune cell infiltration analysis were conducted through SRplot and TIMER database, respectively. Survival association was studied using Cox proportional regression and Kaplan-Meier analysis.

Results

A significant downregulation of AQP1, AQP8, AQP11, AQP12A and AQP12B expression and upregulation of AQP5, AQP6 and AQP9 expression were observed in PAAD (-value = 0.0001). This analysis revealed that overexpression of AQP6 was significantly associated with the poor outcome of the PAAD patients (HR=1.8399, =0.037). Additionally, we found that alcohol history and low expression of AQP1 and AQP9 were associated with low survival among the PAAD patients and these aquaporins were strongly correlated with immune infiltrates.

Discussion

Our research underscores the important role of aquaporins, especially AQP6, in pancreatic adenocarcinoma prognosis. The correlation of AQP1 and AQP9 with immune cell infiltration and patient survival indicates their promise as immuno-oncological markers. These results validate the use of aquaporins as diagnostic and prognostic targets in PAAD treatment.

Conclusion

Our results suggested that AQP6 might be a novel prognostic marker in PAAD patients. Additionally, AQP12A and AQP12B may act as distinctive diagnostic markers to detect pancreatic adenocarcinoma.

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References

  1. BrayF. LaversanneM. SungH. FerlayJ. SiegelR.L. SoerjomataramI. JemalA. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202474322926310.3322/caac.2183438572751
     [Google Scholar]
  2. MizrahiJ.D. SuranaR. ValleJ.W. ShroffR.T. Pancreatic cancer.Lancet2020395102422008202010.1016/S0140‑6736(20)30974‑032593337
     [Google Scholar]
  3. BallehaninnaU.K. ChamberlainR.S. Serum CA 19-9 as a biomarker for pancreatic cancer: A comprehensive review.Indian J. Surg. Oncol.2011228810010.1007/s13193‑011‑0042‑122693400
     [Google Scholar]
  4. DajaniS. SaripalliA. Sharma-WaliaN. Water transport proteins-aquaporins (AQPs) in cancer biology.Oncotarget2018991363923640510.18632/oncotarget.2635130555637
     [Google Scholar]
  5. DireitoI. PaulinoJ. VigiaE. BritoM.A. SoveralG. Differential expression of aquaporin-3 and aquaporin-5 in pancreatic ductal adenocarcinoma.J. Surg. Oncol.2017115898099610.1002/jso.2460528471475
     [Google Scholar]
  6. Bruun-SørensenA.S. EdamanaS. LoginF.H. BorgquistS. NejsumL.N. Aquaporins in pancreatic ductal adenocarcinoma.Acta Pathol. Microbiol. Scand. Suppl.20211291270070510.1111/apm.1318434582595
     [Google Scholar]
  7. MagouliotisD.E. TasiopoulouV.S. DimasK. SakellaridisN. SvokosK.A. SvokosA.A. ZacharoulisD. Transcriptomic analysis of the Aquaporin (AQP) gene family interactome identifies a molecular panel of four prognostic markers in patients with pancreatic ductal adenocarcinoma.Pancreatology201919343644210.1016/j.pan.2019.02.00630826259
     [Google Scholar]
  8. da SilvaI.V. GarraS. CalamitaG. SoveralG. The multifaceted role of aquaporin-9 in health and its potential as a clinical biomarker.Biomolecules202212789710.3390/biom1207089735883453
     [Google Scholar]
  9. LiuX. XuQ. LiZ. XiongB. Integrated analysis identifies AQP9 correlates with immune infiltration and acts as a prognosticator in multiple cancers.Sci. Rep.20201012079510.1038/s41598‑020‑77657‑z33247170
     [Google Scholar]
  10. ColapricoA. SilvaT.C. OlsenC. GarofanoL. CavaC. GaroliniD. SabedotT.S. MaltaT.M. PagnottaS.M. CastiglioniI. CeccarelliM. BontempiG. NoushmehrH. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data.Nucleic Acids Res.2016448e7110.1093/nar/gkv150726704973
     [Google Scholar]
  11. LonsdaleJ. ThomasJ. SalvatoreM. PhillipsR. LoE. ShadS. HaszR. WaltersG. GarciaF. YoungN. FosterB. MoserM. KarasikE. GillardB. RamseyK. SullivanS. BridgeJ. MagazineH. SyronJ. FlemingJ. SiminoffL. TrainoH. MosavelM. BarkerL. JewellS. RohrerD. MaximD. FilkinsD. HarbachP. CortadilloE. BerghuisB. TurnerL. HudsonE. FeenstraK. SobinL. RobbJ. BrantonP. KorzeniewskiG. ShiveC. TaborD. QiL. GrochK. NampallyS. BuiaS. ZimmermanA. SmithA. BurgesR. RobinsonK. ValentinoK. BradburyD. CosentinoM. Diaz-MayoralN. KennedyM. EngelT. WilliamsP. EricksonK. ArdlieK. WincklerW. GetzG. DeLucaD. MacArthurD. KellisM. ThomsonA. YoungT. GelfandE. DonovanM. MengY. GrantG. MashD. MarcusY. BasileM. LiuJ. ZhuJ. TuZ. CoxN.J. NicolaeD.L. GamazonE.R. ImH.K. KonkashbaevA. PritchardJ. StevensM. FlutreT. WenX. DermitzakisE.T. LappalainenT. GuigoR. MonlongJ. SammethM. KollerD. BattleA. MostafaviS. McCarthyM. RivasM. MallerJ. RusynI. NobelA. WrightF. ShabalinA. FeoloM. SharopovaN. SturckeA. PaschalJ. AndersonJ.M. WilderE.L. DerrL.K. GreenE.D. StruewingJ.P. TempleG. VolpiS. BoyerJ.T. ThomsonE.J. GuyerM.S. NgC. AbdallahA. ColantuoniD. InselT.R. KoesterS.E. LittleA.R. BenderP.K. LehnerT. YaoY. ComptonC.C. VaughtJ.B. SawyerS. LockhartN.C. DemchokJ. MooreH.F. GTEx Consortium The Genotype-Tissue Expression (GTEx) project.Nat. Genet.201345658058510.1038/ng.265323715323
     [Google Scholar]
  12. ThanguduR.R. RudnickP.A. HolckM. SinghalD. MacCossM.J. EdwardsN.J. KetchumK.A. KinsingerC.R. KimE. BasuA. Abstract LB-242: Proteomic data commons: A resource for proteogenomic analysis.Cancer Res.20208016_SupplementLB-242[abstract]10.1158/1538‑7445.AM2020‑LB‑242
     [Google Scholar]
  13. GaoJ. AksoyB.A. DogrusozU. DresdnerG. GrossB. SumerS.O. SunY. JacobsenA. SinhaR. LarssonE. CeramiE. SanderC. SchultzN. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.Sci. Signal.20136269pl110.1126/scisignal.200408823550210
     [Google Scholar]
  14. NgP.C. HenikoffS. SIFT: Predicting amino acid changes that affect protein function.Nucleic Acids Res.200331133812381410.1093/nar/gkg50912824425
     [Google Scholar]
  15. ChoiY. ChanA.P. PROVEAN web server: A tool to predict the functional effect of amino acid substitutions and indels.Bioinformatics201531162745274710.1093/bioinformatics/btv19525851949
     [Google Scholar]
  16. AdzhubeiI JordanDM SunyaevSR Predicting functional effect of human missense mutations using PolyPhen-2.Curr Protoc Hum Genet2013767.20.110.1002/0471142905.hg0720s76
     [Google Scholar]
  17. CapriottiE. FariselliP. PhD-SNPg: A webserver and lightweight tool for scoring single nucleotide variants.Nucleic Acids Res.201745W1W247W25210.1093/nar/gkx36928482034
     [Google Scholar]
  18. KangJ. TangQ. HeJ. LiL. YangN. YuS. WangM. ZhangY. LinJ. CuiT. HuY. TanP. ChengJ. ZhengH. WangD. SuX. ChenW. HuangY. RNAInter v4.0: RNA interactome repository with redefined confidence scoring system and improved accessibility.Nucleic Acids Res.202250D1D326D33210.1093/nar/gkab99734718726
     [Google Scholar]
  19. ShannonP. MarkielA. OzierO. BaligaN.S. WangJ.T. RamageD. AminN. SchwikowskiB. IdekerT. Cytoscape: A software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.123930314597658
     [Google Scholar]
  20. TangD. ChenM. HuangX. ZhangG. ZengL. ZhangG. WuS. WangY. SRplot: A free online platform for data visualization and graphing.PLoS One20231811e029423610.1371/journal.pone.029423637943830
     [Google Scholar]
  21. LiT. FuJ. ZengZ. CohenD. LiJ. ChenQ. LiB. LiuX.S. TIMER2.0 for analysis of tumor-infiltrating immune cells.Nucleic Acids Res.202048W1W509W51410.1093/nar/gkaa40732442275
     [Google Scholar]
  22. TerryM.T. PatriciaM.G. Modeling Survival Data: Extending the Cox Model.New YorkSpringer2000
     [Google Scholar]
  23. WangS. ZhengY. YangF. ZhuL. ZhuX.Q. WangZ.F. WuX.L. ZhouC.H. YanJ.Y. HuB.Y. KongB. FuD.L. BrunsC. ZhaoY. QinL.X. DongQ.Z. The molecular biology of pancreatic adenocarcinoma: Translational challenges and clinical perspectives.Signal Transduct. Target. Ther.20216124910.1038/s41392‑021‑00659‑434219130
     [Google Scholar]
  24. VareedayahA.A. AlkaadeS. TaylorJ.R. Pancreatic adenocarcinoma.Mo. Med.2018115323023530228728
     [Google Scholar]
  25. KaneL.E. MellotteG.S. MylodE. O’BrienR.M. O’ConnellF. BuckleyC.E. ArlowJ. NguyenK. MocklerD. MeadeA.D. RyanB.M. MaherS.G. Diagnostic accuracy of blood-based biomarkers for pancreatic cancer: A systematic review and meta-analysis.Cancer Res. Commun.20222101229124310.1158/2767‑9764.CRC‑22‑019036969742
     [Google Scholar]
  26. VerkmanA.S. Mammalian aquaporins: Diverse physiological roles and potential clinical significance.Expert Rev. Mol. Med.200810e1310.1017/S146239940800069018482462
     [Google Scholar]
  27. WangZ. WangY. HeY. ZhangN. ChangW. NiuY. Aquaporin-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation.Anim. Cells Syst.202024525325910.1080/19768354.2020.183398533209198
     [Google Scholar]
  28. SunW.J. HuD.H. WuH. XiaoH. LuM.D. GuoW.J. HuangH. YuY.J. HuT.Y. ZhengZ.Q. Expression of AQP1 was associated with apoptosis and survival of patients in gastric adenocarcinoma.Dig. Surg.201633319019610.1159/00044384326866931
     [Google Scholar]
  29. YunS. SunP.L. JinY. KimH. ParkE. ParkS.Y. LeeK. LeeK. ChungJ.H. Aquaporin 1 is an independent marker of poor prognosis in lung adenocarcinoma.J. Pathol. Transl. Med.201650425125710.4132/jptm.2016.03.3027271108
     [Google Scholar]
  30. HoqueM.O. SoriaJ.C. WooJ. LeeT. LeeJ. JangS.J. UpadhyayS. TrinkB. MonittoC. DesmazeC. MaoL. SidranskyD. MoonC. Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth.Am. J. Pathol.200616841345135310.2353/ajpath.2006.05059616565507
     [Google Scholar]
  31. LopesP.A. FonsecaE. da SilvaI.V. VigiaE. PaulinoJ. SoveralG. Aquaporins transcripts with potential prognostic value in pancreatic cancer.Genes2023149169410.3390/genes1409169437761834
     [Google Scholar]
  32. WeiM. YuH. ZhangY. ZengJ. CaiC. ShiR. Decreased expression of aquaporin 1 correlates with clinicopathological features of patients with cervical cancer.OncoTargets Ther.2019122843285110.2147/OTT.S19465031118662
     [Google Scholar]
  33. LeeS. KimB. JungM. MoonK.C. Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study.J. Pathol. Transl. Med.202357423223710.4132/jptm.2023.06.1737460397
     [Google Scholar]
  34. GuoK. JinF. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression.Biochem. Biophys. Res. Commun.2015465364464910.1016/j.bbrc.2015.08.07826299924
     [Google Scholar]
  35. PustA. KyliesD. Hube-MaggC. KluthM. MinnerS. KoopC. GrobT. GraefenM. SalomonG. TsourlakisM.C. IzbickiJ. WittmerC. HulandH. SimonR. WilczakW. SauterG. SteurerS. KrechT. SchlommT. MellingN. Aquaporin 5 expression is frequent in prostate cancer and shows a dichotomous correlation with tumor phenotype and PSA recurrence.Hum. Pathol.20164810211010.1016/j.humpath.2015.09.02626614400
     [Google Scholar]
  36. ZhouJ. DongY. LiuJ. RenJ. WuJ. ZhuN. AQP5 regulates the proliferation and differentiation of epidermal stem cells in skin aging.Braz. J. Med. Biol. Res.20205311e1000910.1590/1414‑431x20201000932965322
     [Google Scholar]
  37. LoginF.H. PalmfeldtJ. CheahJ.S. YamadaS. NejsumL.N. Aquaporin-5 regulation of cell–cell adhesion proteins: An elusive “tail” story.Am. J. Physiol. Cell Physiol.20213203C282C29210.1152/ajpcell.00496.202033175575
     [Google Scholar]
  38. ChenC. MaT. ZhangC. ZhangH. BaiL. KongL. LuoJ. Down-regulation of aquaporin 5- mediated epithelial-mesenchymal transition and anti-metastatic effect by natural product Cairicoside E in colorectal cancer.Mol. Carcinog.201756122692270510.1002/mc.2271228833571
     [Google Scholar]
  39. ChenG. SongH. YangZ. DuT. ZhengY. LuZ. ZhangK. WeiD. AQP5 is a novel prognostic biomarker in pancreatic adenocarcinoma.Front. Oncol.20221289019310.3389/fonc.2022.89019335619903
     [Google Scholar]
  40. PellavioG. MartinottiS. PatroneM. RanzatoE. LaforenzaU. Aquaporin-6 may increase the resistance to oxidative stress of malignant pleural mesothelioma cells.Cells20221112189210.3390/cells1112189235741021
     [Google Scholar]
  41. MaJ. ZhouC. YangJ. DingX. ZhuY. ChenX. Expression of AQP6 and AQP8 in epithelial ovarian tumor.J. Mol. Histol.201647212913410.1007/s10735‑016‑9657‑426779650
     [Google Scholar]
  42. YamamotoE. JooK. LeeJ. SansomM.S.P. YasuiM. Molecular mechanism of anion permeation through aquaporin 6.Biophys. J.2024123162496250510.1016/j.bpj.2024.06.01338894539
     [Google Scholar]
  43. IshibashiK. KuwaharaM. GuY. KageyamaY. TohsakaA. SuzukiF. MarumoF. SasakiS. Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol, and urea.J. Biol. Chem.199727233207822078610.1074/jbc.272.33.207829252401
     [Google Scholar]
  44. DaiC. CharlestinV. WangM. WalkerZ.T. Miranda-VergaraM.C. FacchineB.A. WuJ. KalineyW.J. DovichiN.J. LiJ. LittlepageL.E. Aquaporin-7 regulates the response to cellular stress in breast cancer.Cancer Res.202080194071408610.1158/0008‑5472.CAN‑19‑226932631905
     [Google Scholar]
  45. BhattacharjeeA. JanaA. BhattacharjeeS. MitraS. DeS. AlghamdiB.S. AlamM.Z. MahmoudA.B. Al ShareefZ. Abdel-RahmanW.M. Woon-KhiongC. AlexiouA. PapadakisM. AshrafG.M. The role of Aquaporins in tumorigenesis: Implications for therapeutic development.Cell Commun. Signal.202422110610.1186/s12964‑023‑01459‑938336645
     [Google Scholar]
  46. MoonC.S. MoonD. KangS.K. Aquaporins in cancer biology.Front. Oncol.20221278282910.3389/fonc.2022.78282935847914
     [Google Scholar]
  47. NagarajuG.P. BashaR. RajithaB. AleseO.B. AlamA. PattnaikS. El-RayesB. Aquaporins: Their role in gastrointestinal malignancies.Cancer Lett.20163731121810.1016/j.canlet.2016.01.00326780474
     [Google Scholar]
  48. ThapaS. ChetryM. HuangK. PengY. WangJ. WangJ. ZhouY. ShenY. XueY. JiK. Significance of aquaporins’ expression in the prognosis of gastric cancer.Biosci. Rep.2018383BSR2017168710.1042/BSR2017168729678898
     [Google Scholar]
  49. SegaF.V.D. ZamboninL. FiorentiniD. RizzoB. CalicetiC. LandiL. HreliaS. PrataC. Specific aquaporins facilitate Nox-produced hydrogen peroxide transport through plasma membrane in leukaemia cells.Biochim. Biophys. Acta Mol. Cell Res.20141843480681410.1016/j.bbamcr.2014.01.01124440277
     [Google Scholar]
  50. ZhangL. LiJ. ZongL. ChenX. ChenK. JiangZ. NanL. LiX. LiW. ShanT. MaQ. MaZ. Reactive oxygen species and targeted therapy for pancreatic cancer.Oxid. Med. Cell. Longev.201620161161678110.1155/2016/161678126881012
     [Google Scholar]
  51. BadautJ. RegliL. Distribution and possible roles of aquaporin 9 in the brain.Neuroscience2004129496997910.1016/j.neuroscience.2004.06.03515561412
     [Google Scholar]
  52. IshibashiK. KuwaharaM. GuY. TanakaY. MarumoF. SasakiS. Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol.Biochem. Biophys. Res. Commun.1998244126827410.1006/bbrc.1998.82529514918
     [Google Scholar]
  53. XuW.H. ShiS.N. XuY. WangJ. WangH.K. CaoD.L. ShiG.H. QuY.Y. ZhangH.L. YeD.W. Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma.J. Transl. Med.201917136310.1186/s12967‑019‑2113‑y31703694
     [Google Scholar]
  54. GaoC. ShenJ. YaoL. XiaZ. LiangX. ZhuR. ChenZ. Low expression of AQP9 and its value in hepatocellular carcinoma.Transl. Cancer Res.20211041826184110.21037/tcr‑20‑315835116505
     [Google Scholar]
  55. ChenQ. ZhuL. ZhengB. WangJ. SongX. ZhengW. WangL. YangD. WangJ. Effect of AQP9 expression in androgen-independent prostate cancer cell PC3.Int. J. Mol. Sci.201617573810.3390/ijms1705073827187384
     [Google Scholar]
  56. OliveiraL.G. Souza-TestasiccaM.C. RicottaT.N.Q. VagoJ.P. dos SantosL.M. CrepaldiF. LimaK.M. Queiroz-JuniorC. SousaL.P. FernandesA.P. Temporary shutdown of ERK1/2 phosphorylation is associated with activation of adaptive immune cell responses and disease progression during Leishmania amazonensis infection in BALB/c Mice.Front. Immunol.20221376208010.3389/fimmu.2022.76208035145518
     [Google Scholar]
  57. ZhuX. JinX. LiZ. ChenX. ZhaoJ. miR-152–3p facilitates cell adhesion and hepatic metastases in colorectal cancer via targeting AQP11.Pathol. Res. Pract.202324415438910.1016/j.prp.2023.15438936889174
     [Google Scholar]
  58. KimH. BhattacharyaA. QiL. Endoplasmic reticulum quality control in cancer: Friend or foe.Semin. Cancer Biol.201533253310.1016/j.semcancer.2015.02.00325794824
     [Google Scholar]
  59. CutlerC.P. BenderJ. ConnerS. OmoregieE. Aquaporin 12 is expressed in the stomach and liver of the spiny dogfish (Squalus acanthias). J. Mar. Sci. Eng.202513116110.3390/jmse13010161
     [Google Scholar]
  60. ItohT. RaiT. KuwaharaM. KoS.B.H. UchidaS. SasakiS. IshibashiK. Identification of a novel aquaporin, AQP12, expressed in pancreatic acinar cells.Biochem. Biophys. Res. Commun.2005330383283810.1016/j.bbrc.2005.03.04615809071
     [Google Scholar]
  61. ParkS.E. KimN.D. YooY.H. Acetylcholinesterase plays a pivotal role in apoptosome formation.Cancer Res.20046482652265510.1158/0008‑5472.CAN‑04‑064915087373
     [Google Scholar]
  62. HuJ.X. ZhaoC.F. ChenW.B. LiuQ.C. LiQ.W. LinY.Y. GaoF. Pancreatic cancer: A review of epidemiology, trend, and risk factors.World J. Gastroenterol.202127274298432110.3748/wjg.v27.i27.429834366606
     [Google Scholar]
  63. EdenbergH.J. The genetics of alcohol metabolism: Role of alcohol dehydrogenase and aldehyde dehydrogenase variants.Alcohol Res. Health200730151317718394
     [Google Scholar]
  64. AlbertsonD.G. Gene amplification in cancer.Trends Genet.200622844745510.1016/j.tig.2006.06.00716787682
     [Google Scholar]
  65. NgambenjawongC. GustafsonH.H. PunS.H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics.Adv. Drug Deliv. Rev.201711420622110.1016/j.addr.2017.04.01028449873
     [Google Scholar]
  66. RenL. LiP. LiZ. ChenQ. AQP9 and ZAP70 as immune-related prognostic biomarkers suppress proliferation, migration and invasion of laryngeal cancer cells.BMC Cancer202222146510.1186/s12885‑022‑09458‑835477402
     [Google Scholar]
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Prognostic Assessment of Aquaporins in Pancreatic Adenocarcinoma: An In Silico Analysis
Curr. Biotechnol. 14, 130 (2025); https://doi.org/10.2174/0122115501371592250411055637
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  • Article Type:     Research Article
Keyword(s): Pancreatic adenocarcinoma, aquaporins, prognostic marker, diagnostic marker, immune infiltration, poor survival, alcohol history

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