{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:51:40Z","timestamp":1776210700266,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000738","name":"University of Leicester","doi-asserted-by":"publisher","award":["Future 100"],"award-info":[{"award-number":["Future 100"]}],"id":[{"id":"10.13039\/501100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The identification and targeting of lung-cancer-cell-surface proteins are important for drug development. Molecularly imprinted polymer nanoparticles (nanoMIPs) offer a synthetic approach for the recognition of proteins on the cell surfaces. This work outlines the use of a novel \u2018snapshot imprinting\u2019 approach to characterize differences in the cell-surface proteomes of lung cancer cell lines (A549, H460, H522) and a non-cancerous cell line (BEAS-2B) to potential protein targets for diagnostic and therapeutic applications. The mass spectrometry-based quantitative proteomics identified 2381 proteins. Fold change and p-value thresholds were used to define statistically and biologically significant differentially expressed proteins (DEPs) across cell lines, yielding 353, 426, and 274 DEPs for A549, H460, and H522, respectively, when compared to BEAS-2B. The DEPs identified across overlapping cell line comparisons were analyzed using Gene Ontology enrichment and a protein\u2013protein network to identify hub proteins. Among these hub proteins, five proteins (NPM1, TOP2A, EZH2, PRKDC, and HNRNPK) were identified as clinically relevant when cross-referenced with the Human Protein Atlas database and the literature, highlighting their potential as diagnostic and therapeutic targets. These findings highlight the potential of nanoMIP-based snapshot imprinting as an alternative to \u2018classical\u2019 approaches for identifying potential protein targets for diagnostic and therapeutic applications.<\/jats:p>","DOI":"10.3390\/polym18020281","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T17:20:42Z","timestamp":1768929642000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecularly Imprinted Polymer Nanoparticles for Lung-Cancer-Cell-Surface Proteomics"],"prefix":"10.3390","volume":"18","author":[{"given":"Kirabo","family":"Magumba","sequence":"first","affiliation":[{"name":"School of Chemistry, College of Science and Engineering, University of Leicester, Leicester LE2 7RH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Piletska","sequence":"additional","affiliation":[{"name":"School of Chemistry, College of Science and Engineering, University of Leicester, Leicester LE2 7RH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6559-0836","authenticated-orcid":false,"given":"Thong Huy","family":"Cao","sequence":"additional","affiliation":[{"name":"Leicester van Geest MultiOMICs Facility, University of Leicester, Leicester LE3 9QP, UK"},{"name":"Division of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK"},{"name":"National Institute for Health and Care Research, Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester LE3 9QP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-870X","authenticated-orcid":false,"given":"Donald","family":"Jones","sequence":"additional","affiliation":[{"name":"Leicester van Geest MultiOMICs Facility, University of Leicester, Leicester LE3 9QP, UK"},{"name":"Leicester Cancer Research Centre, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-8840","authenticated-orcid":false,"given":"Salvador","family":"Macip","sequence":"additional","affiliation":[{"name":"Mechanisms of Cancer and Aging Laboratory, Division of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK"},{"name":"FoodLab, eHealth Centre, Faculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, Spain"},{"name":"Biology of Neurodegeneration and Ageing Research Group, BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2052-5763","authenticated-orcid":false,"given":"Sergey","family":"Piletsky","sequence":"additional","affiliation":[{"name":"School of Chemistry, College of Science and Engineering, University of Leicester, Leicester LE2 7RH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"S38","article-title":"Analysis of Diagnostic Delay and its Impact on Lung Cancer Survival: Results from the Spanish Thoracic Tumor Registry","volume":"60","author":"Cobo","year":"2024","journal-title":"Arch. Bronconeumol. (Engl. Ed.)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jprot.2016.08.006","article-title":"Integral membrane proteins in proteomics. How to break open the black box?","volume":"153","author":"Vit","year":"2017","journal-title":"J. Proteom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101304","DOI":"10.1016\/j.nantod.2021.101304","article-title":"Snapshot imprinting: Rapid identification of cancer cell surface proteins and epitopes using molecularly imprinted polymers","volume":"41","author":"Piletsky","year":"2021","journal-title":"Nano Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3892\/mmr.2021.12530","article-title":"Shuttling of cellular proteins between the plasma membrane and nucleus","volume":"25","author":"Zheng","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105569","DOI":"10.1016\/j.pep.2020.105569","article-title":"Production of membrane proteins in industry: The example of GPCRs","volume":"169","author":"Errey","year":"2020","journal-title":"Protein Expr. Purif."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jprot.2013.03.035","article-title":"Surfomics: Shaving live organisms for a fast proteomic identification of surface proteins","volume":"97","year":"2014","journal-title":"J. Proteom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/14789450.2018.1429924","article-title":"Cell-surface proteomics for the identification of novel therapeutic targets in cancer","volume":"15","author":"Kuhlmann","year":"2018","journal-title":"Expert Rev. Proteom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/jssc.201900700","article-title":"An overview on enrichment methods for cell surface proteome profiling","volume":"43","author":"Li","year":"2020","journal-title":"J. Sep. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1021\/ac0354037","article-title":"Proteomic Analysis of Integral Plasma Membrane Proteins","volume":"76","author":"Zhao","year":"2004","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12575-016-0043-0","article-title":"Reliable FASP-based procedures for optimal quantitative proteomic and phosphoproteomic analysis on samples from acute myeloid leukemia patients","volume":"18","author":"Mjaavatten","year":"2016","journal-title":"Biol. Proced. Online"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Mann","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1476-4598-12-11","article-title":"Combining phenotypic and proteomic approaches to identify membrane targets in a \u2018triple negative\u2019 breast cancer cell type","volume":"12","author":"Rust","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17747","DOI":"10.1039\/D2RA01830F","article-title":"Molecular imprinting as a tool for determining molecular markers: A lung cancer case","volume":"12","author":"Piletska","year":"2022","journal-title":"RSC Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1039\/D2NA00424K","article-title":"Snapshot imprinting as a tool for surface mapping and identification of novel biomarkers of senescent cells","volume":"4","author":"Piletska","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chin, C., Chen, S., Wu, H., Ho, C., Ko, M., and Lin, C. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nprot.2016.030","article-title":"Solid-phase synthesis of molecularly imprinted nanoparticles","volume":"11","author":"Canfarotta","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1038\/s41467-022-31810-6","article-title":"The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance","volume":"13","author":"Ferguson","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40164-025-00603-0","article-title":"Targeting secretory autophagy in solid cancers: Mechanisms, immune regulation and clinical insights","volume":"14","author":"Li","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100692","DOI":"10.1016\/j.mcpro.2023.100692","article-title":"Secretome Analysis: Reading Cellular Sign Language to Understand Intercellular Communication","volume":"23","author":"Wu","year":"2024","journal-title":"Mol. Cell. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Qiu, L., Ma, Z., and Wu, X. (2024). Mutant p53-Mediated Tumor Secretome: Bridging Tumor Cells and Stromal Cells. Genes, 15.","DOI":"10.3390\/genes15121615"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.cell.2023.03.010","article-title":"The role of extracellular vesicles in cancer","volume":"186","author":"Kalluri","year":"2023","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1002\/mco2.70009","article-title":"Extracellular vesicles in cancers: Mechanisms, biomarkers, and therapeutic strategies","volume":"5","author":"Ma","year":"2024","journal-title":"MedComm"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10555-020-09936-0","article-title":"Targeting the cytoskeleton against metastatic dissemination","volume":"40","author":"Ruggiero","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, E.J., Chen, I., Kuo, B.Y., Yu, C., Lai, M., Lin, J., Lin, L.Y., Chen, C., Hwang, T., and Sheu, J.J. (2022). Alterations of Cytoskeleton Networks in Cell Fate Determination and Cancer Development. Biomolecules, 12.","DOI":"10.3390\/biom12121862"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3892\/or.2023.8563","article-title":"Nucleophosmin promotes lung adenocarcinoma cell proliferation, migration and invasion by activating the EGFR\/MAPK signaling pathway","volume":"49","author":"Li","year":"2023","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/j.1349-7006.1998.tb00640.x","article-title":"Differential Expression of DNA Topoisomerase II\u03b1 and II\u03b2 Genes between Small Cell and Non-small Cell Lung Cancer","volume":"89","author":"Syahruddin","year":"1998","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrc2608","article-title":"DNA topoisomerase II and its growing repertoire of biological functions","volume":"9","author":"Nitiss","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s12935-019-0956-1","article-title":"Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis","volume":"19","author":"Ma","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12228","DOI":"10.1038\/s41598-024-63055-2","article-title":"Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer","volume":"14","author":"Wu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/14728222.2025.2482555","article-title":"Enhancer of zeste homolog 2 (EZH2) in endocrine tumors: Current knowledge and future directions","volume":"29","author":"Kumari","year":"2025","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114313","DOI":"10.1016\/j.biopha.2023.114313","article-title":"The pharmacological and biological importance of EZH2 signaling in lung cancer","volume":"160","author":"Entezari","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fan, K., Zhang, B., Han, D., and Sun, Y. (2023). EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates. BMC Bioinform., 24.","DOI":"10.1186\/s12859-023-05271-7"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.prp.2017.04.002","article-title":"Clinicopathological significance and prognostic role of EZH2 expression in non-small cell lung cancer","volume":"213","author":"Kim","year":"2017","journal-title":"Pathol. Res. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101313","DOI":"10.1016\/j.gendis.2024.101313","article-title":"Treating human cancer by targeting EZH2","volume":"12","author":"Xu","year":"2025","journal-title":"Genes Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1158\/2767-9764.CRC-23-0399","article-title":"EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell","volume":"4","author":"DuCote","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e29628","DOI":"10.1097\/MD.0000000000029628","article-title":"Potential value of PRKDC as a therapeutic target and prognostic biomarker in pan-cancer","volume":"101","author":"Yang","year":"2022","journal-title":"Medicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1186\/s12935-021-02229-8","article-title":"Role of PRKDC in cancer initiation, progression, and treatment","volume":"21","author":"Chen","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e000485","DOI":"10.1136\/jitc-2019-000485","article-title":"PRKDC: New biomarker and drug target for checkpoint blockade immunotherapy","volume":"8","author":"Tan","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e33143","DOI":"10.1097\/MD.0000000000033143","article-title":"Expression and prognostic impact of DNA-PK in human lung cancer","volume":"102","author":"Tirilomi","year":"2023","journal-title":"Medicine"},{"key":"ref_44","first-page":"22","article-title":"Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment","volume":"1","author":"Hsu","year":"2012","journal-title":"Transl. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1016\/j.apsb.2021.07.029","article-title":"DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_46","first-page":"728","article-title":"A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours","volume":"124","author":"Awada","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5065","DOI":"10.1038\/s41467-019-12836-9","article-title":"Cadogan AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity","volume":"10","author":"Jacqueline","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1111\/1759-7714.14387","article-title":"Heterogeneous nuclear ribonucleoprotein K promotes the progression of lung cancer by inhibiting the p53-dependent signaling pathway","volume":"13","author":"Li","year":"2022","journal-title":"Thorac. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15046","DOI":"10.1074\/jbc.M113.466136","article-title":"Heterogeneous Nuclear Ribonucleoprotein K (hnRNP-K) Promotes Tumor Metastasis by Induction of Genes Involved in Extracellular Matrix, Cell Movement, and Angiogenesis","volume":"288","author":"Gao","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1038\/s41467-019-12238-x","article-title":"HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/2\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:15:30Z","timestamp":1769058930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/2\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["polym18020281"],"URL":"https:\/\/doi.org\/10.3390\/polym18020281","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}