{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T16:08:14Z","timestamp":1764691694709,"version":"3.46.0"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT-Foundation for Science and Technology"},{"name":"PPBI-Portuguese Platform of BioImaging research unit","award":["POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022122"]}]},{"name":"Portuguese NMR Network","award":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013-PINFRA\/22161\/2016"]}]},{"name":"Research Unit on Applied Molecular Biosciences-UCIBIO","award":["UIDP\/04378\/2020","UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020","UIDB\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy-i4HB","award":["2022.04315.PTDC"],"award-info":[{"award-number":["2022.04315.PTDC"]}]},{"name":"NRC-LPCC Bolsa Rocha Alves 2022","award":["2473"],"award-info":[{"award-number":["2473"]}]},{"name":"EATRIS, the European infrastructure for translational medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Background\/Objectives: Late diagnosis hampers effective treatment of non-small cell lung cancer (NSCLC). This study evaluated whether circulating microRNAs (miRs), miR-155 and miR-3196, measured in liquid biopsy peripheral blood mononuclear cells (PBMCs), can serve as potential non-invasive biomarkers for NSCLC diagnosis, patient stratification, therapy monitoring, and prognosis. Methods: RNA was isolated from PBMCs of 136 NSCLC patients and 64 healthy donors. RT\u2013qPCR quantified miR expression in PBMCs after predefined QC filtering: miR-155-3p (NSCLC n = 63; controls n = 28), miR-3196 (NSCLC n = 55; controls n = 28), and miR-155-5p (NSCLC n = 23; controls n = 12). Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses, reporting area under the curve (AUC), and threshold-dependent sensitivity\/specificity. Survival was analyzed with Kaplan\u2013Meier\/Cox methods. Associations with clinicopathological variables (stage, metastasis, smoking, EGFR, and KRAS status), treatment response (chemotherapy, immunotherapy, TKIs), and survival outcomes were examined. Results: miR-155-3p was upregulated in NSCLC, whereas miR-3196 was downregulated relative to controls; AUCs were 0.881 and 0.784, respectively. At high-sensitivity operating points, specificity was lower (\u224829\u201330%), consistent with PBMC miRs reflecting both immune activation and tumor burden. In adenocarcinoma, miR-155-3p was associated with advanced stage, metastatic disease and smoking history. miR-3196 aligned with features of metastatic progression. During systemic therapy (chemotherapy, immunotherapy, TKIs), circulating levels of both miRs tended to normalize. Notably, normalization of miR-155-3p levels was associated with improved overall survival, supporting its prognostic value and utility for treatment monitoring. Conclusions: Circulating miR-155-3p and miR-3196 in PBMCs are promising screening\/monitoring non-invasive candidates rather than stand-alone NSCLC diagnostics at current thresholds. Combining these miRs with additional biomarkers and\/or clinical covariates and tuning decision thresholds may enhance specificity for diagnostic use. While preliminary, these findings warrant validation in large, prospective studies with standardized protocols to enable clinical implementation.<\/jats:p>","DOI":"10.3390\/biomedicines13122946","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:31:46Z","timestamp":1764689506000},"page":"2946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["miRNA-155-3p and miRNA-3196 as Potential Biomarkers in Liquid Biopsies of Non-Small Cell Lung Cancer Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Daniela","family":"Alexandre","sequence":"first","affiliation":[{"name":"RISE-Health, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"},{"name":"UCIBIO, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"i4HB, Associate Laboratory\u2014Institute for Health and Bioeconomy, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Joana","family":"Polido","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-2003","authenticated-orcid":false,"given":"Salete","family":"Valente","sequence":"additional","affiliation":[{"name":"ULS Cova Beira, Servi\u00e7o de Pneumologia, 6200-251 Covilh\u00e3, Portugal"}]},{"given":"Daniel Pimenta","family":"Rocha","sequence":"additional","affiliation":[{"name":"ULS Cova Beira, Servi\u00e7o de Pneumologia, 6200-251 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-4438","authenticated-orcid":false,"given":"Alexandra R.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"UCIBIO, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"i4HB, Associate Laboratory\u2014Institute for Health and Bioeconomy, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-7095","authenticated-orcid":false,"given":"Pedro V.","family":"Baptista","sequence":"additional","affiliation":[{"name":"UCIBIO, Department of Life Sciences, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"},{"name":"i4HB, Associate Laboratory\u2014Institute for Health and Bioeconomy, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-1242","authenticated-orcid":false,"given":"Carla","family":"Cruz","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Chemistry, Faculty of Sciences, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"},{"name":"Departamento de Qu\u00edmica, University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"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. 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