Skip to content
2000
image of A Comprehensive Analysis of the Clinical Significance and Underlying Oncogenic Roles of Specific MMPs in Gastric Carcinoma Reveals their Potential Roles in Prognosis and Therapy

Abstract

Background

Gastric cancer is a major global cause of cancer-related deaths, necessitating investigation into Matrix Metalloproteinases’ (MMPs) diagnostic and prognostic value. Our study aimed to analyze their significance in gastric cancer.

Methods

We evaluated MMP family genes' mRNA and protein expression using the University of Alabama at Birmingham (UALCAN) and Human Protein Atlas (HPA) databases. Then, we analyzed the relationship between their mRNA expression and gastric cancer staging and survival using Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter. Furthermore, we assessed this family’s gene mutation rates in gastric cancer patients using Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) and explored potential pathways and mechanisms Database for Annotation, Visualization, and Integrated Discovery (DAVID), cBioPortal, and R. Finally, we established a predictive model for gastric cancer based on these analyses to understand these genes’ roles in cancer.

Results

Our findings revealed significantly upregulated mRNA expression of MMP1/2/3/7/9/10/11/12/13/14 in gastric cancer tissues (p<0.05). Higher levels of MMP2/7/10-encoded proteins (middle or high) were observed in tumor tissues, with MMP2/11/14 closely associated with different cancer stages (p<0.05). Additionally, MMP2/7/11/14/20 mRNA levels correlated with short-term overall survival (about 20 months), while MMP1/3/9/12/13 expression was associated with favorable overall survival (about 30 months). Gastric cancer patients exhibited a 21% mutation rate of MMP family genes, which correlated with favorable overall survival. Enrichment analysis and protein-protein interaction results underscored the close association of MMPs with gastric cancer development. The MMP2 model demonstrated a significant decline in survival rates for the high expression group, with a Hazard Ratio (HR) of 1.78 (95% CI 1.47-2.16) and a log-rank P value of 2.9e-09. Statistical significance was set at p < 0.05. Univariate Cox regression identified MMP2 as a risk factor for gastric cancer patients.

Conclusion

Our findings highlighted MMPs' essential role in gastric cancer progression, impacting patient survival. MMP2 emerged as a promising target for gastric carcinoma detection and treatment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240309837241204184939
2025-01-03
2025-09-14

  • From This Site

    /content/journals/cmm/10.2174/0115665240309837241204184939
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  2. Cao W. Chen H.D. Yu Y.W. Li N. Chen W.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J. (Engl.) 2021 134 7 783 791 10.1097/CM9.0000000000001474 33734139
    [Google Scholar]
  3. Joshi S.S. Badgwell B.D. Current treatment and recent progress in gastric cancer. CA Cancer J. Clin. 2021 71 3 264 279 10.3322/caac.21657 33592120
    [Google Scholar]
  4. Ajucarmelprecilla A. Pandi J. Dhandapani R. Ramanathan S. Chinnappan J. Paramasivam R. Thangavelu S. Mohammed Ghilan A.K. Aljohani S.A.S. Oyouni A.A.A. Farasani A. Altayar M.A. Althagafi H.A.E. Alzahrani O.R. Durairaj K. Shrestha A. In silico identification of hub genes as observing biomarkers for gastric cancer metastasis. Evid. Based Complement. Alternat. Med. 2022 2022 1 12 10.1155/2022/6316158 35535159
    [Google Scholar]
  5. Chinnappan J. Ramu A. v V.R. S A.K. Integrative bioinformatics approaches to therapeutic gene target selection in various cancers for Nitroglycerin. Sci. Rep. 2021 11 1 22036 10.1038/s41598‑021‑01508‑8 34764329
    [Google Scholar]
  6. Smyth E.C. Nilsson M. Grabsch H.I. van Grieken N.C.T. Lordick F. Gastric cancer. Lancet 2020 396 10251 635 648 10.1016/S0140‑6736(20)31288‑5 32861308
    [Google Scholar]
  7. Yeoh K.G. Tan P. Mapping the genomic diaspora of gastric cancer. Nat. Rev. Cancer 2021 34702982
    [Google Scholar]
  8. Overall C.M. Kleifeld O. Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer 2006 6 3 227 239 10.1038/nrc1821 16498445
    [Google Scholar]
  9. Dufour A. Overall C.M. Missing the target: Matrix metalloproteinase antitargets in inflammation and cancer. Trends Pharmacol. Sci. 2013 34 4 233 242 10.1016/j.tips.2013.02.004 23541335
    [Google Scholar]
  10. Liu J. Chen T. Li S. Liu W. Wang P. Shang G. Targeting matrix metalloproteinases by E3 ubiquitin ligases as a way to regulate the tumor microenvironment for cancer therapy. Semin. Cancer Biol. 2022 86 Pt 2 259 268 10.1016/j.semcancer.2022.06.004 35724822
    [Google Scholar]
  11. Alaseem A. Alhazzani K. Dondapati P. Alobid S. Bishayee A. Rathinavelu A. Matrix metalloproteinases: A challenging paradigm of cancer management. Semin. Cancer Biol. 2019 56 100 115 10.1016/j.semcancer.2017.11.008 29155240
    [Google Scholar]
  12. Mustafa S. Koran S. AlOmair L. Insights into the role of matrix metalloproteinases in cancer and its various therapeutic aspects: A review. Front. Mol. Biosci. 2022 9 896099 10.3389/fmolb.2022.896099 36250005
    [Google Scholar]
  13. Yue B. Biology of the extracellular matrix: An overview. J. Glaucoma 2014 23 8 Suppl 1 S20 S23 10.1097/IJG.0000000000000108 25275899
    [Google Scholar]
  14. Surguchev A.A. Emamzadeh F.N. Surguchov A. Cell responses to extracellular α-synuclein. Molecules 2019 24 2 305 10.3390/molecules24020305 30650656
    [Google Scholar]
  15. Csapo R. Gumpenberger M. Wessner B. Skeletal muscle extracellular matrix – What do we know about its composition, regulation, and physiological roles? A narrative review. Front. Physiol. 2020 11 253 10.3389/fphys.2020.00253 32265741
    [Google Scholar]
  16. Lu P. Takai K. Weaver V.M. Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb. Perspect. Biol. 2011 3 12 a005058 10.1101/cshperspect.a005058 21917992
    [Google Scholar]
  17. Cabral-Pacheco G.A. Garza-Veloz I. Castruita-De la Rosa C. Ramirez-Acuña J.M. Perez-Romero B.A. Guerrero-Rodriguez J.F. Martinez-Avila N. Martinez-Fierro M.L. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci. 2020 21 24 9739 10.3390/ijms21249739 33419373
    [Google Scholar]
  18. Shay G. Lynch C.C. Fingleton B. Moving targets: Emerging roles for MMPs in cancer progression and metastasis. Matrix Biol. 2015 44-46 200 206 10.1016/j.matbio.2015.01.019 25652204
    [Google Scholar]
  19. Walker C. Mojares E. Del Río Hernández A. Role of extracellular matrix in development and cancer progression. Int. J. Mol. Sci. 2018 19 10 3028 10.3390/ijms19103028 30287763
    [Google Scholar]
  20. Jacob A. Prekeris R. The regulation of MMP targeting to invadopodia during cancer metastasis. Front. Cell Dev. Biol. 2015 3 4 10.3389/fcell.2015.00004 25699257
    [Google Scholar]
  21. Łukaszewicz-Zając M. Mroczko B. Szmitkowski M. Gastric cancer — The role of matrix metalloproteinases in tumor progression. Clin. Chim. Acta 2011 412 19-20 1725 1730 10.1016/j.cca.2011.06.003 21693112
    [Google Scholar]
  22. Zheng H. Takahashi H. Murai Y. Cui Z. Nomoto K. Niwa H. Tsuneyama K. Takano Y. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res. 2006 26 5A 3579 3583 17094486
    [Google Scholar]
  23. Ii M. Yamamoto H. Adachi Y. Maruyama Y. Shinomura Y. Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp. Biol. Med. (Maywood) 2006 231 1 20 27 10.1177/153537020623100103 16380641
    [Google Scholar]
  24. Chandrashekar D.S. Bashel B. Balasubramanya S.A.H. Creighton C.J. Ponce-Rodriguez I. Chakravarthi B.V.S.K. Varambally S. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 2017 19 8 649 658 10.1016/j.neo.2017.05.002 28732212
    [Google Scholar]
  25. Yang Q. Hong K. Li Y. Shi P. Yan F. Zhang P. Receptor-interacting protein kinase 2 is associated with tumor immune infiltration, immunotherapy-related biomarkers, and affects gastric cancer cells growth in vivo. J. Cancer 2024 15 1 176 191 10.7150/jca.90008 38164277
    [Google Scholar]
  26. Ma T. Ma N. Chen J.L. Tang F.X. Zong Z. Yu Z.M. Chen S. Zhou T.C. Expression and prognostic value of Chromobox family members in gastric cancer. J. Gastrointest. Oncol. 2020 11 5 983 998 10.21037/jgo‑20‑223 33209492
    [Google Scholar]
  27. Rao X. Jiang J. Liang Z. Zhang J. Zhuang Z. Qiu H. Luo H. Weng N. Wu X. Down-regulated CLDN10 predicts favorable prognosis and correlates with immune infiltration in gastric cancer. Front. Genet. 2021 12 747581 10.3389/fgene.2021.747581 34721537
    [Google Scholar]
  28. Asplund A. Edqvist P.H.D. Schwenk J.M. Pontén F. Antibodies for profiling the human proteome — The Human protein atlas as a resource for cancer research. Proteomics 2012 12 13 2067 2077 10.1002/pmic.201100504 22623277
    [Google Scholar]
  29. Lánczky A. Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): Development and implementation. J. Med. Internet Res. 2021 23 7 e27633 10.2196/27633 34309564
    [Google Scholar]
  30. Fu D. Wang C. Yu L. Yu R. Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling. Cell. Mol. Biol. Lett. 2021 26 1 26 10.1186/s11658‑021‑00271‑y 34098867
    [Google Scholar]
  31. Cerami E. Gao J. Dogrusoz U. Gross B.E. Sumer S.O. Aksoy B.A. Jacobsen A. Byrne C.J. Heuer M.L. Larsson E. Antipin Y. Reva B. Goldberg A.P. Sander C. Schultz N. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012 2 5 401 404 10.1158/2159‑8290.CD‑12‑0095 22588877
    [Google Scholar]
  32. Gao J. Aksoy B.A. Dogrusoz U. Dresdner G. Gross B. Sumer S.O. Sun Y. Jacobsen A. Sinha R. Larsson E. Cerami E. Sander C. Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 2013 6 269 pl1 10.1126/scisignal.2004088 23550210
    [Google Scholar]
  33. Tang Z. Li C. Kang B. Gao G. Li C. Zhang Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017 45 W1 W98 W102 10.1093/nar/gkx247 28407145
    [Google Scholar]
  34. Huang DW. Sherman BT. Tan Q. DAVID bioinformatics resources: Expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007 35 Web Server issue W169 W175 10.1093/nar/gkm415 17576678
    [Google Scholar]
  35. Huang D.W. Sherman B.T. Lempicki R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 2009 4 1 44 57 10.1038/nprot.2008.211 19131956
    [Google Scholar]
  36. Guo J.Y. Jing Z. Li X. Liu L. Bioinformatic analysis identifying PSMB 1/2/3/4/6/8/9/10 as prognostic indicators in clear cell renal cell carcinoma. Int. J. Med. Sci. 2022 19 5 796 812 10.7150/ijms.71152 35693739
    [Google Scholar]
  37. Li S. Pritchard D.M. Yu L.G. Regulation and function of matrix metalloproteinase-13 in cancer progression and metastasis. Cancers (Basel) 2022 14 13 3263 10.3390/cancers14133263 35805035
    [Google Scholar]
  38. Wątroba S. Wiśniowski T. Bryda J. Kurzepa J. The role of matrix metalloproteinases in pathogenesis of human bladder cancer. Acta Biochim. Pol. 2021 68 4 547 555 10.18388/abp.2020_5600 34314132
    [Google Scholar]
  39. Siddhartha R. Garg M. Molecular and clinical insights of matrix metalloproteinases into cancer spread and potential therapeutic interventions. Toxicol. Appl. Pharmacol. 2021 426 115593 10.1016/j.taap.2021.115593 34038713
    [Google Scholar]
  40. Pezeshkian Z. Nobili S. Peyravian N. Shojaee B. Nazari H. Soleimani H. Asadzadeh-Aghdaei H. Ashrafian Bonab M. Nazemalhosseini-Mojarad E. Mini E. Insights into the role of matrix metalloproteinases in precancerous conditions and in colorectal cancer. Cancers (Basel) 2021 13 24 6226 10.3390/cancers13246226 34944846
    [Google Scholar]
  41. Lin H. Xu P. Huang M. Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments. Future Med. Chem. 2022 14 1 35 51 10.4155/fmc‑2021‑0246 34779649
    [Google Scholar]
  42. Gonzalez-Avila G. Sommer B. García-Hernandez A.A. Ramos C. Flores-Soto E. Nanotechnology and matrix metalloproteinases in cancer diagnosis and treatment. Front. Mol. Biosci. 2022 9 918789 10.3389/fmolb.2022.918789 35720130
    [Google Scholar]
  43. Sokolova O. Naumann M. Matrix metalloproteinases in Helicobacter pylori–associated gastritis and gastric cancer. Int. J. Mol. Sci. 2022 23 3 1883 10.3390/ijms23031883 35163805
    [Google Scholar]
  44. Niland S. Riscanevo A.X. Eble J.A. Matrix metalloproteinases shape the tumor microenvironment in cancer progression. Int. J. Mol. Sci. 2021 23 1 146 10.3390/ijms23010146 35008569
    [Google Scholar]
  45. Gonzalez-Avila G. Sommer B. Mendoza-Posada D.A. Ramos C. Garcia-Hernandez A.A. Falfan-Valencia R. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit. Rev. Oncol. Hematol. 2019 137 57 83 10.1016/j.critrevonc.2019.02.010 31014516
    [Google Scholar]
  46. Kaczorowska A. Miękus N. Stefanowicz J. Adamkiewicz-Drożyńska E. Selected matrix metalloproteinases (MMP-2, MMP-7) and their inhibitor (TIMP-2) in adult and pediatric cancer. Diagnostics (Basel) 2020 10 8 547 10.3390/diagnostics10080547 32751899
    [Google Scholar]
  47. Zhong Y. Lu Y.T. Sun Y. Shi Z.H. Li N.G. Tang Y.P. Duan J.A. Recent opportunities in matrix metalloproteinase inhibitor drug design for cancer. Expert Opin. Drug Discov. 2018 13 1 75 87 10.1080/17460441.2018.1398732 29088927
    [Google Scholar]
  48. Liu C. Li Y. Hu S. Chen Y. Gao L. Liu D. Guo H. Yang Y. Clinical significance of matrix metalloproteinase-2 in endometrial cancer. Medicine (Baltimore) 2018 97 29 e10994 10.1097/MD.0000000000010994 30024495
    [Google Scholar]
  49. Tauro M. Lynch C. Cutting to the chase: How matrix metalloproteinase-2 activity controls breast-cancer-to-bone metastasis. Cancers (Basel) 2018 10 6 185 10.3390/cancers10060185 29874869
    [Google Scholar]
  50. Chen L. Li M. Li Q. Wang C. Xie S. DKK1 promotes hepatocellular carcinoma cell migration and invasion through β-catenin/MMP7 signaling pathway. Mol. Cancer 2013 12 1 157 10.1186/1476‑4598‑12‑157 24325363
    [Google Scholar]
  51. Hemers E. Duval C. McCaig C. Handley M. Dockray G.J. Varro A. Insulin-like growth factor binding protein-5 is a target of matrix metalloproteinase-7: Implications for epithelial-mesenchymal signaling. Cancer Res. 2005 65 16 7363 7369 10.1158/0008‑5472.CAN‑05‑0157 16103088
    [Google Scholar]
  52. Miyata Y. Iwata T. Ohba K. Kanda S. Nishikido M. Kanetake H. Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: Prognostic implications and clinical significance for invasion and metastasis. Clin. Cancer Res. 2006 12 23 6998 7003 10.1158/1078‑0432.CCR‑06‑1626 17145820
    [Google Scholar]
  53. Kenji S.F. Kurma K. Collet B. Oblet C. Debure L. Di Primo C. Minder L. Vérité F. Danger Y. Jean M. Penna A. Levoin N. Legembre P. MMP7 cleavage of amino-terminal CD95 death receptor switches signaling toward non-apoptotic pathways. Cell Death Dis. 2022 13 10 895 10.1038/s41419‑022‑05352‑0 36274061
    [Google Scholar]
  54. Liao H.Y. Da C.M. Liao B. Zhang H.H. Roles of matrix metalloproteinase-7 (MMP-7) in cancer. Clin. Biochem. 2021 92 9 18 10.1016/j.clinbiochem.2021.03.003 33713636
    [Google Scholar]
  55. Huachuan Z. Xiaohan L. Jinmin S. Qian C. Yan X. Yinchang Z. Expression of matrix metalloproteinase-7 involving in growth, invasion, metastasis and angiogenesis of gastric cancer. Chin. Med. Sci. J. 2003 18 2 80 86 12903787
    [Google Scholar]
  56. Koskensalo S. Mrena J. Wiksten J.P. Nordling S. Kokkola A. Hagström J. Haglund C. MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol. 2010 31 3 149 155 10.1007/s13277‑010‑0020‑1 20300917
    [Google Scholar]
  57. Abdel-Hamid N.M. Abass S.A. Matrix metalloproteinase contribution in management of cancer proliferation, metastasis and drug targeting. Mol. Biol. Rep. 2021 48 9 6525 6538 10.1007/s11033‑021‑06635‑z 34379286
    [Google Scholar]
  58. Mondal S. Adhikari N. Banerjee S. Amin S.A. Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur. J. Med. Chem. 2020 194 112260 10.1016/j.ejmech.2020.112260 32224379
    [Google Scholar]
  59. Cai N. Cheng K. Ma Y. Liu S. Tao R. Li Y. Li D. Guo B. Jia W. Liang H. Zhao J. Xia L. Ding Z. Chen J. Zhang W. Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8 + T cell-mediated antitumour immunity and improves anti-PD-1 efficacy. Gut 2024 73 6 985 999 10.1136/gutjnl‑2023‑331342 38123979
    [Google Scholar]
  60. Karreman M.A. Bauer A.T. Solecki G. Berghoff A.S. Mayer C.D. Frey K. Hebach N. Feinauer M.J. Schieber N.L. Tehranian C. Mercier L. Singhal M. Venkataramani V. Schubert M.C. Hinze D. Hölzel M. Helfrich I. Schadendorf D. Schneider S.W. Westphal D. Augustin H.G. Goetz J.G. Schwab Y. Wick W. Winkler F. Active remodeling of capillary endothelium via cancer cell–derived MMP9 promotes metastatic brain colonization. Cancer Res. 2023 83 8 1299 1314 10.1158/0008‑5472.CAN‑22‑3964 36652557
    [Google Scholar]
  61. McCarty J.H. MMP9 clears the way for metastatic cell penetration across the blood–brain barrier. Cancer Res. 2023 83 8 1167 1169 10.1158/0008‑5472.CAN‑23‑0151 37057598
    [Google Scholar]
  62. Dong H. Diao H. Zhao Y. Xu H. Pei S. Gao J. Wang J. Hussain T. Zhao D. Zhou X. Lin D. Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling. Cell Prolif. 2019 52 5 e12633 10.1111/cpr.12633 31264317
    [Google Scholar]
  63. Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors (Basel) 2018 18 10 3249 10.3390/s18103249 30262739
    [Google Scholar]
  64. Zhang Z. Ge H. Micrometastasis in gastric cancer. Cancer Lett. 2013 336 1 34 45 10.1016/j.canlet.2013.04.021 23624301
    [Google Scholar]
  65. Hashemi M. Aparviz R. Beickzade M. Paskeh M.D.A. Kheirabad S.K. Koohpar Z.K. Moravej A. Dehghani H. Saebfar H. Zandieh M.A. Salimimoghadam S. Rashidi M. Taheriazam A. Entezari M. Samarghandian S. Advances in RNAi therapies for gastric cancer: Targeting drug resistance and nanoscale delivery. Biomed. Pharmacother. 2023 169 115927 10.1016/j.biopha.2023.115927 38006616
    [Google Scholar]
  66. Li D. Xu M. Wang Z. Huang P. Huang C. Chen Z. Tang G. Zhu X. Cai M. Qin S. The EMT-induced lncRNA NR2F1-AS1 positively modulates NR2F1 expression and drives gastric cancer via miR-29a-3p/VAMP7 axis. Cell Death Dis. 2022 13 1 84 10.1038/s41419‑022‑04540‑2 35082283
    [Google Scholar]
  67. Zhou Y. Zhou B. Pache L. Chang M. Khodabakhshi A.H. Tanaseichuk O. Benner C. Chanda S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 2019 10 1 1523 10.1038/s41467‑019‑09234‑6 30944313
    [Google Scholar]
  68. Quintero-Fabián S. Arreola R. Becerril-Villanueva E. Torres-Romero J.C. Arana-Argáez V. Lara-Riegos J. Ramírez-Camacho M.A. Alvarez-Sánchez M.E. Role of matrix metalloproteinases in angiogenesis and cancer. Front. Oncol. 2019 9 1370 10.3389/fonc.2019.01370 31921634
    [Google Scholar]
  69. Gwee Y.X. Chia D.K.A. So J. Ceelen W. Yong W.P. Tan P. Ong C.A.J. Sundar R. Integration of genomic biology into therapeutic strategies of gastric cancer peritoneal metastasis. J. Clin. Oncol. 2022 40 24 2830 10.1200/JCO.21.02745 35649219
    [Google Scholar]
  70. Nakajima T. Konda Y. Kanai M. Izumi Y. Kanda N. Nanakin A. Kitazawa S. Chiba T. Prohormone convertase furin has a role in gastric cancer cell proliferation with parathyroid hormone-related peptide in a reciprocal manner. Dig. Dis. Sci. 2002 47 12 2729 2737 10.1023/A:1021005221934 12498293
    [Google Scholar]
  71. Guan X. Zhao H. Niu J. Tan D. Ajani J.A. Wei Q. Polymorphisms of TGFB1 and VEGF genes and survival of patients with gastric cancer. J. Exp. Clin. Cancer Res. 2009 28 1 94 10.1186/1756‑9966‑28‑94 19566948
    [Google Scholar]
  72. Hou W. Kong L. Hou Z. Ji H. CD44 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer. BMC Med. Genomics 2022 15 1 225 10.1186/s12920‑022‑01383‑w 36316684
    [Google Scholar]
  73. Zhang Y. Zhou M. Wei H. Zhou H. He J. Lu Y. Wang D. Chen B. Zeng J. Peng W. Du F. Gong A. Xu M. Furin promotes epithelial-mesenchymal transition in pancreatic cancer cells via Hippo-YAP pathway. Int. J. Oncol. 2017 50 4 1352 1362 10.3892/ijo.2017.3896 28259973
    [Google Scholar]
  74. Försti A. Li X. Wagner K. Tavelin B. Enquist K. Palmqvist R. Altieri A. Hallmans G. Hemminki K. Lenner P. Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression. Genes Chromosomes Cancer 2010 49 3 270 281 10.1002/gcc.20738 19998449
    [Google Scholar]
  75. Blanchette F. Rudd P. Grondin F. Attisano L. Dubois C.M. Involvement of Smads in TGFβ1‐induced furin (fur) transcription. J. Cell. Physiol. 2001 188 2 264 273 10.1002/jcp.1116 11424093
    [Google Scholar]
  76. Zeng J. Yang L. Zeng L. Feng C. Yang Y. Ye Y. Zhang W. He J. Zhang C. Visualizing cancer resistance via nano-quenching and recovery detector of CD44. J. Nanobiotechnology 2024 22 1 452 10.1186/s12951‑024‑02732‑w 39080641
    [Google Scholar]
  77. Lordick F. Shitara K. Janjigian Y.Y. New agents on the horizon in gastric cancer. Ann. Oncol. 2017 28 8 1767 1775 10.1093/annonc/mdx051 28184417
    [Google Scholar]
  78. Alsina M. Arrazubi V. Diez M. Tabernero J. Current developments in gastric cancer: From molecular profiling to treatment strategy. Nat. Rev. Gastroenterol. Hepatol. 2022 36344677
    [Google Scholar]
  79. Lei Z.N. Teng Q.X. Tian Q. Chen W. Xie Y. Wu K. Zeng Q. Zeng L. Pan Y. Chen Z.S. He Y. Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduct. Target. Ther. 2022 7 1 358 10.1038/s41392‑022‑01190‑w 36209270
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240309837241204184939
Loading
A Comprehensive Analysis of the Clinical Significance and Underlying Oncogenic Roles of Specific MMPs in Gastric Carcinoma Reveals their Potential Roles in Prognosis and Therapy
Bentham Science Publishers ; https://doi.org/10.2174/0115665240309837241204184939
/content/journals/cmm/10.2174/0115665240309837241204184939
/content/journals/cmm/10.2174/0115665240309837241204184939
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: predictive modeling ; molecular targeted therapy ; matrix metalloproteinase ; Gastric cancer ; biomarkers

Most Cited Most Cited RSS feed

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