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This study performed next-generation sequencing to globally profile serum miRNAs from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition controls, identifying 28 upregulated miRNAs and implicating them in NSCLC signaling pathways. A gradient-boosting decision tree trained on 2588 miRNAs achieved strong discrimination, further refined by Shapley Additive explanations selecting the top 15 miRNAs, improving model performance. 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Cell Lung Cancer  \nRadoslaw Charkiewicz 1,2, *,†, Anetta Sulewska 2,†, Robert Mroz 3, Alicja Charkiewicz 4, Wojciech Naumnik 5, Marcin Kraska 2,6, Attila Gyenesei 7, Bence Galik 7, Sini Junttila 8, Borys Miskiewicz 9, Rafal Stec 10,  \nPiotr Karabowicz 11, Magdalena Zawada 12, Wojciech Miltyk 4 and Jacek Niklinski 2, *  \nCitation: Charkiewicz, R.; Sulewska, A.; Mroz, R.; Charkiewicz, A.; Naumnik, W.; Kraska, M.; Gyenesei, A.; Galik, B.; Junttila, S.; Miskiewicz, B.; et al. Serum Insights: Leveraging the Power of miRNA Profiling as an Early Diagnostic Tool for Non-Small Cell Lung Cancer. Cancers 2023, 15, 4910. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15204910  \nAcademic Editor: Akiteru Goto  \nReceived: 2 August 2023  \nRevised: 5 October 2023  \nAccepted: 8 October 2023  \nPublished: 10 October 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Center of Experimental Medicine, Medical University of Bialystok, 15-369 Bialystok, Poland  \n2 Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland; [anetta.sulewska@umb.edu.pl](anetta.sulewska@umb.edu.pl) (A.S.); [marcin.kraska92@gmail.com](marcin.kraska92@gmail.com) (M.K.)  \n3 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, Poland; [robert.mroz@umb.edu.pl](robert.mroz@umb.edu.pl)  \n4 Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; [alicja.charkiewicz@umb.edu.pl](alicja.charkiewicz@umb.edu.pl) (A.C.); [wojciech.miltyk@umb.edu.pl](wojciech.miltyk@umb.edu.pl) (W.M.)  \n5 1st Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, Poland; [wojciech.naumnik@umb.edu.pl](wojciech.naumnik@umb.edu.pl)  \n6 Department of Medical Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland  \n7 Szentagothai Research Center, Genomic and Bioinformatic Core Facility, H-7624 Pecs, Hungary; [gyenesei.attila@pte.hu](gyenesei.attila@pte.hu) (A.G.); [galik.bence@pte.hu](galik.bence@pte.hu) (B.G.)  \n8 Turku Bioscience Centre, University of Turku & Åbo Akademi University, FI-20520 Turku, Finland;  \nsimaju@utu.fi  \n9 Department of Thoracic Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland; [borys.miskiewicz@uskwb.pl](borys.miskiewicz@uskwb.pl)  \n10 Department of Oncology, Medical University of Warsaw, 02-091 Warsaw, Poland; [rafal.stec@uckwum.edu.pl](rafal.stec@uckwum.edu.pl)  \n11 Biobank, Medical University of Bialystok, 15-269 Bialystok, Poland; [piotr.karabowicz@umb.edu.pl](piotr.karabowicz@umb.edu.pl)  \n[12](12 Department of Hematology Diagnostics and Genetics)[ Department of Hematology Diagnostics and Genetics](12 Department of Hematology Diagnostics and Genetics), [The University Hospital](The University Hospital), [30-688 Krakow](30-688 Krakow), [Poland](Poland); [mzawada@su.krakow.pl](mzawada@su.krakow.pl)  \n* Correspondence: [radoslaw.charkiewicz@umb.edu.pl](radoslaw.charkiewicz@umb.edu.pl) (R.C.); [jacek.niklinski@umb.edu.pl](jacek.niklinski@umb.edu.pl) (J.N.)† These authors contributed equally to this work.  \nSimple Summary: Non-small cell lung cancer (NSCLC) is a prevalent and lethal disease. Circulating cell-free miRNA has the potential to serve as a biomarker for early detection as it reflects cancer characteristics. Through global miRNA profiling in serum samples from NSCLC patients and noncancerous individuals, we identified 28 upregulated miRNAs in NSCLC and explored their relevance to NSCLC-rela","cbCaidtPG24fqoGs","https://ap.wps.com/l/cbCaidtPG24fqoGs","pdf",3671767,25,"English","# Simple Summary\n# Abstract\n# Citation and Publication Details\n# Methods and Main Findings","[{\"question\":\"What biomarker approach does the study investigate for early NSCLC detection?\",\"answer\":\"The study investigates circulating cell-free serum microRNAs as a potential non-invasive biomarker, using global miRNA profiling to derive a diagnostic signature.\"},{\"question\":\"How were miRNAs profiled and how many samples were used?\",\"answer\":\"Next-generation sequencing was used to globally profile miRNAs in serum from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients.\"},{\"question\":\"What machine-learning method was used to classify NSCLC versus non-cancer cases?\",\"answer\":\"A gradient-boosting decision tree classifier was developed to distinguish NSCLC from non-cancerous individuals using a large miRNA feature set.\"}]","Serum Insights - Leveraging the Power of miRNA Profiling as an Early Diagnostic Tool for Non-Small Cell Lung Cancer | PDF",1790229637,63]