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NALCN is a sodium leak channel involved in tumor evolution and immunity and has tumor-suppressor functions. This study examines NALCN promoter methylation in aza-treated cell lines, paired NSCLC tissues, and patient plasma ctDNA using a highly specific real-time MSP method. NALCN promoter hypermethylation correlates with worse disease-free intervals and is detectable at low rates in early and advanced cases, supporting epigenetic inactivation as a metastasis predictor.",{"@graph":69,"@context":127},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nalcn-promoter-methylation-as-a-biomarker-for-metastatic-risk-in-a-cohort-of-non-small-cell-lung-cancer-patients/329710/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/nalcn-promoter-methylation-as-a-biomarker-for-metastatic-risk-in-a-cohort-of-non-small-cell-lung-cancer-patients/329710.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-13","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main purpose of evaluating NALCN promoter methylation in NSCLC?","Question",{"text":113,"@type":114},"To determine whether NALCN promoter methylation can serve as a prognostic DNA methylation biomarker and a predictor of metastasis in non-small cell lung cancer.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was NALCN promoter methylation assessed in this study?",{"text":118,"@type":114},"NALCN promoter methylation was measured using a newly developed highly specific and sensitive real-time MSP method in cell lines, paired NSCLC tissues, and plasma ctDNA.",{"name":120,"@type":111,"acceptedAnswer":121},"What relationship was observed between NALCN promoter hypermethylation and patient outcomes?",{"text":122,"@type":114},"Kaplan–Meier analysis showed that NALCN promoter hypermethylation was associated with worse disease-free intervals (DFIs).",{"name":124,"@type":111,"acceptedAnswer":125},"Was NALCN promoter methylation linked to NALCN expression levels?",{"text":126,"@type":114},"NALCN methylation was not statistically significantly correlated with the corresponding NALCN expression level (p = 0.439).","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},329710,1790119601,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":41,"preview_page_count":4},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article  \nNALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients  \nEleni Thanou 1, Dora Lontra 1, Ioanna Balgouranidou 2, Eleni Efthimiadou 3, Alexandra Delipetrou 1, Emilia Tsaroucha 4, Maria Theodosiou 3, Vassilis Georgoulias 5, Athanasios Kotsakis 6, Evi Lianidou 1 and Athina Markou 1, *  \nCitation: Thanou, E.; Lontra, D.; Balgouranidou, I.; Efthimiadou, E.; Delipetrou, A.; Tsaroucha, E.;  \nTheodosiou, M.; Georgoulias, V.; Kotsakis, A.; Lianidou, E.; et al. NALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients. Biomolecules 2024, 14, 1514. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom14121514  \nAcademic Editor: Viswanathan Natarajan  \nReceived: 25 September 2024  \nRevised: 18 November 2024  \nAccepted: 25 November 2024  \nPublished: 27 November 2024  \nCopyright: © 2024 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 Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, 15771 Athens, Greece; [elenathanou99@gmail.com](elenathanou99@gmail.com) (E.T.); [doralontra@hotmail.gr](doralontra@hotmail.gr) (D.L.); [alexdelipetrou@gmail.com](alexdelipetrou@gmail.com) (A.D.); [lianidou@chem.uoa.gr](lianidou@chem.uoa.gr) (E.L.)  \n2 Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; [ioannabalg@gmail.com](ioannabalg@gmail.com)  \n3 Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece; efthim@chem.uoa.gr (E.E.); [mtheodoss@chem.uoa.gr](mtheodoss@chem.uoa.gr) (M.T.)  \n4 8th Department of Pulmonary Diseases,“Sotiria” General Hospital, 11527 Athens, Greece; [emilygeola@yahoo.gr](emilygeola@yahoo.gr)  \n5 First Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece; [georgulv@otenet.gr](georgulv@otenet.gr)  \n6 Department of Medical Oncology, University General Hospital of Larissa, 41334 Larissa, Greece; [thankotsakis@hotmail.com](thankotsakis@hotmail.com)  \n* Correspondence: [atmarkou@chem.uoa.gr](atmarkou@chem.uoa.gr)  \nSimple Summary: Liquid biopsy allows regular monitoring of cancer progression and response to treatment by analyzing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in plasma. This is the first time that the methylation status of NALCN in NSCLC has beenexamined and correlated with its expression. Thus, the detection of NALCN promoter methylation in NSCLC tumor tissue provides significant prognostic information for patients with NSCLC. However, we strongly believe that the evaluation of NALCN promoter methylation in plasma CTDNA as a non-invasive circulating tumor biomarker should be further investigated in a large and well-defined patient cohort.  \nAbstract: Liquid biopsy enables real-time monitoring of tumor development and response to therapy through the analysis of CTCs and ctDNA. NALCN is a sodium leak channel that is frequently involved in tumor evolution and immunity and acts as a tumor suppressor. Deletion of NALCN has been shown to increase cancer metastasis and the number of CTCs in peripheral blood. In this study, we investigated for the first time NALCN promoter methylation in (a) Aza-treated cell lines (A549, TE671, BT20, and MDA-MB-468),(b) paired NSCLC tissues (n = 22), and (c) plasma cell-free DNA (ctDNA) from patients with NSCLC (early stage n = 39, metastatic n = 39) and DNA from 10 healthy donors (HD) using a newly developed highly specific and sensit","cbCairK0d8qXRYaQ","https://ap.wps.com/l/cbCairK0d8qXRYaQ","pdf",1439192,"English","# Introduction\n## Background on lung cancer and NSCLC\n## Rationale for NALCN promoter methylation as a biomarker","[{\"question\":\"What is the main purpose of evaluating NALCN promoter methylation in NSCLC?\",\"answer\":\"To determine whether NALCN promoter methylation can serve as a prognostic DNA methylation biomarker and a predictor of metastasis in non-small cell lung cancer.\"},{\"question\":\"How was NALCN promoter methylation assessed in this study?\",\"answer\":\"NALCN promoter methylation was measured using a newly developed highly specific and sensitive real-time MSP method in cell lines, paired NSCLC tissues, and plasma ctDNA.\"},{\"question\":\"What relationship was observed between NALCN promoter hypermethylation and patient outcomes?\",\"answer\":\"Kaplan–Meier analysis showed that NALCN promoter hypermethylation was associated with worse disease-free intervals (DFIs).\"},{\"question\":\"Was NALCN promoter methylation linked to NALCN expression levels?\",\"answer\":\"NALCN methylation was not statistically significantly correlated with the corresponding NALCN expression level (p = 0.439).\"}]","NALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients | PDF",1789985278]