{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:21:36Z","timestamp":1789579296452,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGF\u03b2 signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic surgical aspirate fluid for proteomic profiling of glioblastoma able to distinguish molecular features specific of the diverse tumor zones and tumor states, possibly contributing to the understanding of the highly infiltrative capability and recurrent rate of this aggressive brain tumor and opening to potential clinical applications to be further investigated.<\/jats:p>","DOI":"10.3390\/cancers13010030","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T12:19:51Z","timestamp":1608725991000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Glioblastoma CUSA Fluid Protein Profiling: A Comparative Investigation of the Core and Peripheral Tumor Zones"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1830-4849","authenticated-orcid":false,"given":"Giuseppe","family":"La Rocca","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mater Olbia Hospital, 07026 Olbia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-9470","authenticated-orcid":false,"given":"Giorgia Antonia","family":"Simboli","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-2234","authenticated-orcid":false,"given":"Federica","family":"Vincenzoni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Valeria","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario A. 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Gemelli IRCCS, Catholic University, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Sabatino","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mater Olbia Hospital, 07026 Olbia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Desiderio","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d, Consiglio Nazionale delle Ricerche, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2174\/157015912799362733","article-title":"Proteomic Analysis of Glioma Chemoresistance","volume":"10","author":"Suk","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1586\/14789450.2014.939634","article-title":"Towards developing biomarkers for glioblastoma multiforme: A proteomics view","volume":"11","author":"Jayaram","year":"2014","journal-title":"Expert Rev. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97304","DOI":"10.18632\/oncotarget.21937","article-title":"Proteogenomic characterization and integrative analysis of glioblastoma multiforme","volume":"8","author":"Song","year":"2017","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Silantyev, A.S., Falzone, L., Libra, M., Gurina, O.I., Kardashova, K.S., Nikolouzakis, T.K., Nosyrev, A.E., Sutton, C.W., Mitsias, P.D., and Tsatsakis, A. (2019). Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics. Cells, 8.","DOI":"10.3390\/cells8080863"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pirlog, R., Susman, S., Iuga, C., and Florian, I.S. (2019). Proteomic Advances in Glial Tumors through Mass Spectrometry Approaches. Medicina, 55.","DOI":"10.3390\/medicina55080412"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1038\/s41388-020-1308-2","article-title":"Breaking through the glioblastoma micro-environment via extracellular vesicles","volume":"39","author":"Simon","year":"2020","journal-title":"Oncogene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.3389\/fimmu.2019.03137","article-title":"Extracellular Vesicles in Glioblastoma Tumor Microenvironment","volume":"10","author":"Yekula","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1800157","DOI":"10.1002\/pmic.201800157","article-title":"Extracellular Vesicles from Neurosurgical Aspirates Identifies Chaperonin Containing TCP1 Subunit 6A as a Potential Glioblastoma Biomarker with Prognostic Significance","volume":"19","author":"Hallal","year":"2019","journal-title":"Proteomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11060-016-2298-3","article-title":"Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease","volume":"131","author":"Mallawaaratchy","year":"2017","journal-title":"J. Neuro Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/10408363.2019.1700208","article-title":"Extracellular vesicles and their role in glioblastoma","volume":"57","author":"Whitehead","year":"2020","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Feldman, L., Fuchshuber, P., and Jones, D.B. (2012). The SAGES Manual on the Fundamental Use of Surgical Energy (FUSE), Springer.","DOI":"10.1007\/978-1-4614-2074-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3390\/cancers5020357","article-title":"Glioma Surgical Aspirate: A Viable Source of Tumor Tissue for Experimental Research","volume":"5","author":"Day","year":"2013","journal-title":"Cancers"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.clineuro.2018.05.015","article-title":"The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review","volume":"170","author":"Monticelli","year":"2018","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_15","first-page":"153","article-title":"Glioblastoma: From volumetric analysis to molecular predictors","volume":"4","author":"Ius","year":"2020","journal-title":"J. Neurosurg. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.7762\/cnr.2018.7.3.153","article-title":"Links between Serine Biosynthesis Pathway and Epigenetics in Cancer Metabolism","volume":"7","author":"Kim","year":"2018","journal-title":"Clin. Nutr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/neuonc\/now024","article-title":"Glycolysis and the pentose phosphate pathway are differentially associated with the dichotomous regulation of glioblastoma cell migration versus proliferation","volume":"18","author":"Schulte","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nn.4537","article-title":"Purine synthesis promotes maintenance of brain tumor initiating cells in glioma","volume":"20","author":"Wang","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0169-328X(96)00058-7","article-title":"Expression of serotonin receptors in human fetal astrocytes and glioma cell lines: A possible role in glioma cell proliferation and migration","volume":"41","author":"Merzak","year":"1996","journal-title":"Mol. Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3390\/neuroglia1020020","article-title":"In Search of a Breakthrough Therapy for Glioblastoma Multiforme","volume":"1","author":"Vasilev","year":"2018","journal-title":"Neuroglia"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Plun-Favreau, H., Lewis, P.A., Hardy, J., Martins, L.M., and Wood, N. (2010). Cancer and Neurodegeneration: Between the Devil and the Deep Blue Sea. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001257"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jocn.2016.05.012","article-title":"The role of CD44 in glioblastoma multiforme","volume":"34","author":"Mooney","year":"2016","journal-title":"J. Clin. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.stem.2014.01.005","article-title":"Osteopontin-CD44 Signaling in the Glioma Perivascular Niche Enhances Cancer Stem Cell Phenotypes and Promotes Aggressive Tumor Growth","volume":"14","author":"Pietras","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1200\/jco.2011.29.15_suppl.2049","article-title":"CD44 as a prognostic and predictive marker for GBM","volume":"29","author":"Vaillant","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_26","first-page":"1","article-title":"Glioblastoma-secreted soluble CD44 activates tau pathology in the brain","volume":"50","author":"Lim","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1172\/JCI121266","article-title":"Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target","volume":"129","author":"Wei","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"D\u2019Alessio, A., Proietti, G., Sica, G., and Scicchitano, B.M. (2019). Pathological and Molecular Features of Glioblastoma and Its Peritumoral Tissue. Cancers, 11.","DOI":"10.3390\/cancers11040469"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2217\/fon-2017-0498","article-title":"CD59: A promising target for tumor immunotherapy","volume":"14","author":"Zhang","year":"2018","journal-title":"Futur. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1016\/S0002-9440(10)63778-9","article-title":"Differential Expression of Splicing Variants of the Human Caldesmon Gene (CALD1) in Glioma Neovascularization versus Normal Brain Microvasculature","volume":"164","author":"Zheng","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaan2507","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Zhang","year":"2017","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/path.2440","article-title":"The Human Protein Atlas\u2014A tool for pathology","volume":"216","author":"Uhlen","year":"2008","journal-title":"J. Pathol."},{"key":"ref_33","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000137285-TUBB2B\/pathology."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1038\/s41598-019-41974-9","article-title":"Metallothionein Genes are Highly Expressed in Malignant Astrocytomas and Associated with Patient Survival","volume":"9","author":"Valiulyte","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-018-0645-x","article-title":"The roles of metallothioneins in carcinogenesis","volume":"11","author":"Si","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1016\/j.celrep.2016.11.012","article-title":"Tenascin-C Orchestrates Glioblastoma Angiogenesis by Modulation of Pro- and Anti-angiogenic Signaling","volume":"17","author":"Rupp","year":"2016","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/neuonc\/nop060","article-title":"Overexpression of ezrin inactivates NF2 tumor suppressor in glioblastoma","volume":"12","author":"Morales","year":"2010","journal-title":"Neuro Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00695","DOI":"10.1016\/j.heliyon.2018.e00695","article-title":"The role of zyxin in regulation of malignancies","volume":"4","author":"Kotb","year":"2018","journal-title":"Heliyon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41374-019-0368-9","article-title":"Zyxin (ZYX) promotes invasion and acts as a biomarker for aggressive phenotypes of human glioblastoma multiforme","volume":"100","author":"Wen","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_40","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000152795-HNRNPDL\/pathology#gene_information."},{"key":"ref_41","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/search\/protein_class:Cancer-related+genes."},{"key":"ref_42","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000117632-STMN1\/pathology."},{"key":"ref_43","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000148672-GLUD1\/pathology."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kutwin, M., Sawosz, E., Jaworski, S., Wierzbicki, M., Strojny, B., Grodzik, M., and Chwalibog, A. (2017). Assessment of the proliferation status of glioblastoma cell and tumour tissue after nanoplatinum treatment. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178277"},{"key":"ref_45","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000008056-SYN1\/pathology#gene_information."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.pneurobio.2010.04.006","article-title":"The synapsins: Key actors of synapse function and plasticity","volume":"91","author":"Cesca","year":"2010","journal-title":"Prog. Neurobiol."},{"key":"ref_47","unstructured":"Conti, F. (2010). Fisiologia Medica 1, Edi. Ermes. [2nd ed.]."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1097\/00001756-200109170-00018","article-title":"Expression of \u03b2-synuclein in normal human astrocytes","volume":"12","author":"Tanji","year":"2001","journal-title":"NeuroReport"},{"key":"ref_49","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000132639-SNAP25\/pathology."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/aob\/mcq243","article-title":"Proliferating cell nuclear antigen (PCNA): A key factor in DNA replication and cell cycle regulation","volume":"107","author":"Strzalka","year":"2010","journal-title":"Ann. Bot."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1242\/jcs.00653","article-title":"Proliferating cell nuclear antigen (PCNA): A dancer with many partners","volume":"116","author":"Maga","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_52","unstructured":"(2019, July 13). Data Available from v19.proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000178802-MPI\/pathology."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D183","DOI":"10.1093\/nar\/gkw1138","article-title":"PANTHER version 11: Expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements","volume":"45","author":"Mi","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_54","unstructured":"(2019, July 09). Accession P00019. Available online: http:\/\/www.pantherdb.org\/pathway\/pathDetail.do?clsAccession=P00019."},{"key":"ref_55","unstructured":"(2019, July 09). Accession P00047. Available online: http:\/\/www.pantherdb.org\/pathway\/pathDetail.do?clsAccession=P00047."},{"key":"ref_56","first-page":"7825","article-title":"Targeting the VEGF and PDGF signaling pathway in glioblastoma treatment","volume":"8","author":"Popescu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106105","DOI":"10.1016\/j.clineuro.2020.106105","article-title":"Contrast enhanced ultrasound (CEUS) applications in neurosurgical and neurological settings\u2014New scenarios for brain and spinal cord ultrasonography. A systematic review","volume":"198","author":"Menna","year":"2020","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_58","first-page":"353","article-title":"Intra-Operative Ultrasound: Tips and Tricks for Making the Most in Neurosurgery","volume":"33","author":"Altieri","year":"2018","journal-title":"Surg. Technol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E529","DOI":"10.1093\/neuros\/nyaa037","article-title":"5-Aminolevulinic Acid and Contrast-Enhanced Ultrasound: The Combination of the Two Techniques to Optimize the Extent of Resection in Glioblastoma Surgery","volume":"86","author":"Ius","year":"2020","journal-title":"Neurosurgery"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.wneu.2019.06.127","article-title":"\u201cEnhancing Vision\u201d in High Grade Glioma Surgery: A Feasible Integrated 5-ALA + CEUS Protocol to Improve Radicality","volume":"129","author":"Sabatino","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_61","first-page":"619","article-title":"State of the art of fluorescence guided techniques in neurosurgery","volume":"63","author":"Menna","year":"2019","journal-title":"J. Neurosurg. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Manini, I., Caponnetto, F., Dalla, E., Ius, T., Della Pepa, G.M., Pegolo, E., Bartolini, A., La Rocca, G., Menna, G., and Di Loreto, C. (2020). Heterogeneity Matters: Different Regions of Glioblastoma Are Characterized by Distinctive Tumor-Supporting Pathways. Cancers, 12.","DOI":"10.3390\/cancers12102960"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1021\/acs.jproteome.6b00392","article-title":"Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1","volume":"15","author":"Deutsch","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-017-1559-2","article-title":"Reactome pathway analysis: A high-performance in-memory approach","volume":"18","author":"Fabregat","year":"2017","journal-title":"BMC Bioinform."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013Protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/1\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:59Z","timestamp":1760179739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/1\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,23]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["cancers13010030"],"URL":"https:\/\/doi.org\/10.3390\/cancers13010030","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,23]]}}}