{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T03:18:37Z","timestamp":1752549517106},"reference-count":40,"publisher":"Croatian Society for Medical Biochemistry and Laboratory Medicine","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. med. (Online)"],"published-print":{"date-parts":[[2023,10,15]]},"abstract":"<jats:p>IntroductionMalignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was to determine whether hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE.\nMaterials and methodsFifty-six patients with MPE and 30 healthy control subjects were included. Computerized tomography (CT) and positron emission tomography (PET) were used to diagnose pleural effusion. Patients with malignant cells in pleural fluid cytological examination were included in the MPE group. Thirty-five patients with lymph node metastases on CT were included in the LNM-positive MPE group. Serum and pleural fluid HIF-1\u03b1 and CD-133 concentrations were measured manually via enzyme-linked immunosorbent assay (ELISA).\nResultsSerum concentrations of HIF-1\u03b1 and CD133 were higher in MPE patients. It was found that CD133\/HIF-1\u03b1 (S) ratio was higher in the malignant patient group with positive lymph node involvement than in the negative group, while concentrations of HIF-1\u03b1 (P) were lower. Pleural fluid HIF-1\u03b1 and CD133\/HIF-1\u03b1 (S) ratio had sufficient performance in diagnosing lymphatic metastases in patients with MPE (AUC = 0.90 and 0.83, respectively).\nConclusionsIn conclusion, serum HIF-1\u03b1 and CD133 concentrations were higher in patients with MPE, consistent with our hypothesis. Concentrations of HIF-1\u03b1 (P) and CD133\/HIF-1\u03b1 (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment.<\/jats:p>","DOI":"10.11613\/bm.2023.030701","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T12:38:16Z","timestamp":1697027896000},"page":"295-304","source":"Crossref","is-referenced-by-count":3,"title":["Clinical importance of serum and pleural fluid prominin-1 and hypoxia-inducible factor-1\u03b1 concentration in the evaluation of lymph node involvement in patients with malignant pleural effusion"],"prefix":"10.11613","volume":"33","author":[{"given":"Mustafa","family":"Kupeli","sequence":"first","affiliation":[{"name":"Department of thoracic surgery, Faculty of medicine, Yozgat Bozok University, Yozgat, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeliha Cansel","family":"Ozmen","sequence":"additional","affiliation":[{"name":"Department of medical biochemistry, Faculty of medicine, Tokat Gaziosmanpa\u015fa University, Tokat, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4885","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"key20231011083709_r1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1183\/16000617.0019-2016","article-title":"Malignant pleural effusion: From bench to bedside.","volume":"25","author":"Psallidas","year":"2016","journal-title":"Eur Respir Rev"},{"key":"key20231011083709_r2","doi-asserted-by":"crossref","first-page":"490","DOI":"10.3390\/medicina55080490","article-title":"Malignant pleural effusion and its current management","volume":"55","author":"Skok","year":"2019","journal-title":"Medicina (Kaunas)"},{"key":"key20231011083709_r3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2147\/CMAR.S95663","article-title":"Management of malignant pleural effusion: Challenges and solutions","volume":"9","author":"Penz","year":"2017","journal-title":"Cancer Manag Res"},{"key":"key20231011083709_r4","first-page":"186","article-title":"Malignant pleural effusions: appropriate treatment approaches.","volume":"41","author":"Aydin","year":"2009","journal-title":"Eurasian J Med"},{"key":"key20231011083709_r5","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1183\/09031936.01.00225601","article-title":"Management of malignant pleural effusions.","volume":"18","author":"Antony","year":"2001","journal-title":"Eur Respir J"},{"key":"key20231011083709_r6","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1073\/pnas.94.23.12425","article-title":"Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells.","volume":"94","author":"Weigmann","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20231011083709_r7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4614-5894-4_1","article-title":"Prominin-1 (CD133): Molecular and cellular features across species.","volume":"777","author":"Corbeil","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"key20231011083709_r8","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.canlet.2007.09.012","article-title":"Influence of oxygen tension on CD133 phenotype in human glioma cell cultures.","volume":"258","author":"Platet","year":"2007","journal-title":"Cancer Lett"},{"key":"key20231011083709_r9","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1634\/stemcells.2006-0398","article-title":"Transcriptional profiling of human cord blood cd133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia.","volume":"25","author":"Martin-Rendon","year":"2007","journal-title":"Stem Cells"},{"key":"key20231011083709_r10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms17071025","article-title":"CD133 modulate HIF-1 \u03b1 expression under hypoxia in EMT phenotype pancreatic cancer stem-like cells.","volume":"17","author":"Maeda","year":"2016","journal-title":"Int J Mol Sci"},{"key":"key20231011083709_r11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/1061186X.2018.1479756","article-title":"CD133: beyond a cancer stem cell biomarker.","volume":"27","author":"Barzegar Behrooz","year":"2019","journal-title":"J Drug Target"},{"key":"key20231011083709_r12","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.","volume":"92","author":"Wang","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20231011083709_r13","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1101\/gad.14.16.1983","article-title":"Hif-1 and human disease: One highly involved factor.","volume":"14","author":"Semenza","year":"2000","journal-title":"Genes Dev"},{"key":"key20231011083709_r14","first-page":"5830","article-title":"Overexpression of hypoxia-inducible factor 1\u03b1 in common human cancers and their metastases.","volume":"59","author":"Zhong","year":"1999","journal-title":"Cancer Res"},{"key":"key20231011083709_r15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.lungcan.2004.02.021","article-title":"Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs).","volume":"45","author":"Ishii","year":"2004","journal-title":"Lung Cancer"},{"key":"key20231011083709_r16","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.2147\/OTT.S199603","article-title":"ASAP3 is a downstream target of HIF-1\u03b1 and is critical for progression of lung adenocarcinoma.","volume":"12","author":"Zhang","year":"2019","journal-title":"Onco Targets Ther"},{"key":"key20231011083709_r17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/mco.2013.195","article-title":"Clinicopathological significance of CD133 in lung cancer: A meta-analysis.","volume":"2","author":"Tan","year":"2014","journal-title":"Mol Clin Oncol"},{"key":"key20231011083709_r18"},{"key":"key20231011083709_r19","doi-asserted-by":"crossref","first-page":"225S","DOI":"10.1378\/chest.89.4_Supplement.225S","article-title":"A New International Staging System for Lung Cancer.","volume":"89","author":"Mountain","year":"1986","journal-title":"Chest"},{"key":"key20231011083709_r20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0021-9681(72)90027-6","article-title":"Indices of relative weight and obesity.","volume":"25","author":"Keys","year":"1972","journal-title":"J Chronic Dis"},{"key":"key20231011083709_r21","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation Coefficients: Appropriate Use and Interpretation.","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth Analg"},{"key":"key20231011083709_r22"},{"key":"key20231011083709_r23"},{"key":"key20231011083709_r24","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s10147-013-0541-x","article-title":"CD133 expression: A potential prognostic marker for non-small cell lung cancers.","volume":"19","author":"Mizugaki","year":"2014","journal-title":"Int J Clin Oncol"},{"key":"key20231011083709_r25","article-title":"Is CD133 expression a prognostic biomarker of non-small-cell lung cancer? a systematic review and meta-analysis.","volume":"9","author":"Wu","year":"2014","journal-title":"PLoS One"},{"key":"key20231011083709_r26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/pro6.16","article-title":"Clinical significance of tumor cells and CD133+ cells from malignant pleural effusion in patients with lung cancer.","volume":"1","author":"Yong","year":"2017","journal-title":"Precis Radiat Oncol"},{"key":"key20231011083709_r27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0021320","article-title":"Spheres derived from lung adenocarcinoma pleural effusions: Molecular characterization and tumor engraftment.","volume":"6","author":"Mancini","year":"2011","journal-title":"PLoS One"},{"key":"key20231011083709_r28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.canlet.2012.03.019","article-title":"Acquisition of an enhanced aggressive phenotype in human lung cancer cells selected by suboptimal doses of cisplatin following cell deattachment and reattachment.","volume":"321","author":"Hsieh","year":"2012","journal-title":"Cancer Lett"},{"key":"key20231011083709_r29","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4049\/jimmunol.149.2.655","article-title":"Soluble forms of CD40 inhibit biologic responses of human B cells.","volume":"149","author":"Fanslow","year":"1992","journal-title":"J Immunol"},{"key":"key20231011083709_r30","first-page":"36","article-title":"Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung cancer: A potential marker of prognosis.","volume":"1","author":"Mu","year":"2015","journal-title":"Chronic Dis Transl Med"},{"key":"key20231011083709_r31","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1158\/0008-5472.CAN-09-1289","article-title":"mTOR signal and hypoxia-inducible factor-1\u03b1 regulate CD133 expression in cancer cells.","volume":"69","author":"Matsumoto","year":"2009","journal-title":"Cancer Res"},{"key":"key20231011083709_r32","article-title":"The expression of hypoxia-inducible factor-1\u03b1 and its clinical significance in lung cancer: A systematic review and meta-analysis.","volume":"143","author":"Ren","year":"2013","journal-title":"Swiss Med Wkly"},{"key":"key20231011083709_r33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1756-9966-30-77","article-title":"HIF-1 effects on angiogenic potential in human small cell lung carcinoma.","volume":"30","author":"Wan","year":"2011","journal-title":"J Exp Clin Cancer Res"},{"key":"key20231011083709_r34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0955-0674(00)00194-0","article-title":"HIF-1 and mechanisms of hypoxia sensing.","volume":"13","author":"Semenza","year":"2001","journal-title":"Curr Opin Cell Biol"},{"key":"key20231011083709_r35","first-page":"32","article-title":"Expression and significance analysis of HIF-1\u03b1 in malignant pleural effusion.","volume":"1","author":"Zibin","year":"2013","journal-title":"Int J Lab Med."},{"key":"key20231011083709_r36","first-page":"1454","article-title":"Research the Expression of GLUT-1 and HIF-1\u03b1 in Malignant Pleural Effusion.","volume":"8","author":"Zang","year":"2012","journal-title":"Chin J Lab Diag."},{"key":"key20231011083709_r37","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/sj.bjc.6601186","article-title":"Overexpression of hypoxia-inducible-factor 1alpha(HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage.","volume":"89","author":"Kurokawa","year":"2003","journal-title":"Br J Cancer"},{"key":"key20231011083709_r38","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/ijc.11068","article-title":"Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma.","volume":"105","author":"Kuwai","year":"2003","journal-title":"Int J Cancer"},{"key":"key20231011083709_r39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.yexmp.2004.11.002","article-title":"Correlation of hypoxia inducible factor-1\u03b1 with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer.","volume":"78","author":"Katsuta","year":"2005","journal-title":"Exp Mol Pathol"},{"key":"key20231011083709_r40","first-page":"8019","article-title":"The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non-small cell lung cancer","volume":"17","author":"Chen","year":"2018","journal-title":"Mol Med Rep"}],"container-title":["Biochemia medica"],"original-title":[],"link":[{"URL":"https:\/\/biochemia-medica.com\/en\/journal\/33\/3\/10.11613\/BM.2023.030701\/fullArticle","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T10:24:01Z","timestamp":1697797441000},"score":1,"resource":{"primary":{"URL":"https:\/\/biochemia-medica.com\/en\/journal\/33\/3\/10.11613\/BM.2023.030701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,10,13]]},"published-print":{"date-parts":[[2023,10,15]]}},"URL":"https:\/\/doi.org\/10.11613\/bm.2023.030701","relation":{},"ISSN":["1846-7482","1330-0962"],"issn-type":[{"value":"1846-7482","type":"electronic"},{"value":"1330-0962","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,13]]}}}