MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma
<b>Background:</b> Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is frequently diagnosed at advanced stages with metastasis, contributing to its poor prognosis. Identifying key metastasis-related biomarkers is critical for improving early diagnos...
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2025-06-01
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| author | Hung-Chih Lai Ju-Fang Liu Tsung-Ming Chang Thai-Yen Ling |
| author_facet | Hung-Chih Lai Ju-Fang Liu Tsung-Ming Chang Thai-Yen Ling |
| author_sort | Hung-Chih Lai |
| collection | DOAJ |
| description | <b>Background:</b> Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is frequently diagnosed at advanced stages with metastasis, contributing to its poor prognosis. Identifying key metastasis-related biomarkers is critical for improving early diagnosis and therapeutic targeting. <b>Methods:</b> We analyzed four GEO microarray datasets (GSE32863, GSE27262, GSE40275, and GSE33356) and TCGA data to identify differentially expressed genes (DEGs) in LUAD. Functional enrichment of DEGs was analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and a Cancer Hallmark Enrichment Plot. Hub gene analysis was conducted using Cytoscape. Hub genes were evaluated for their expression, prognostic significance (via the Kaplan–Meier plotter), and clinical correlation using additional platforms (TCGA, Lung Cancer Explorer, TNMplot, and the Human Protein Atlas). <b>Results:</b> A total of 333 consistently dysregulated DEGs were identified, enriched in pathways related to metastasis, including angiogenesis, immune escape, and ECM interaction. Ten hub genes (<i>AURKA</i>, <i>TOP2A</i>, <i>CCNB2</i>, <i>CENPF</i>, <i>MCM4</i>, <i>TPX2</i>, <i>KIF20A</i>, <i>ASPM</i>, <i>MELK</i>, and <i>NEK2</i>) were identified through network analysis. Among these, <i>MCM4</i> showed strong upregulation in LUAD and was significantly associated with poor overall survival. Notably, <i>MCM4</i> expression also correlated with post-progression survival and markers of invasiveness. Immunohistochemistry and transcriptomic analyses confirmed <i>MCM4</i> overexpression at both mRNA and protein levels. Additionally, <i>MCM4</i> expression was positively correlated with various matrix metalloproteinases, supporting its role in promoting tumor invasiveness. <b>Conclusions:</b> <i>MCM4</i> is a novel potential biomarker for LUAD metastasis and prognosis. Its consistent upregulation, association with metastatic markers, and clinical significance suggest it may serve as a candidate target for diagnostic use or therapeutic intervention in advanced LUAD. |
| format | Article |
| id | doaj-art-d0bf295c606a4ebfb35ea4008ec60760 |
| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj-art-d0bf295c606a4ebfb35ea4008ec607602025-08-20T03:27:01ZengMDPI AGDiagnostics2075-44182025-06-011512155510.3390/diagnostics15121555MCM4 as Potential Metastatic Biomarker in Lung AdenocarcinomaHung-Chih Lai0Ju-Fang Liu1Tsung-Ming Chang2Thai-Yen Ling3Department of Hematology and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111045, TaiwanTranslational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111045, TaiwanSchool of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110301, TaiwanInstitute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100225, Taiwan<b>Background:</b> Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer and is frequently diagnosed at advanced stages with metastasis, contributing to its poor prognosis. Identifying key metastasis-related biomarkers is critical for improving early diagnosis and therapeutic targeting. <b>Methods:</b> We analyzed four GEO microarray datasets (GSE32863, GSE27262, GSE40275, and GSE33356) and TCGA data to identify differentially expressed genes (DEGs) in LUAD. Functional enrichment of DEGs was analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and a Cancer Hallmark Enrichment Plot. Hub gene analysis was conducted using Cytoscape. Hub genes were evaluated for their expression, prognostic significance (via the Kaplan–Meier plotter), and clinical correlation using additional platforms (TCGA, Lung Cancer Explorer, TNMplot, and the Human Protein Atlas). <b>Results:</b> A total of 333 consistently dysregulated DEGs were identified, enriched in pathways related to metastasis, including angiogenesis, immune escape, and ECM interaction. Ten hub genes (<i>AURKA</i>, <i>TOP2A</i>, <i>CCNB2</i>, <i>CENPF</i>, <i>MCM4</i>, <i>TPX2</i>, <i>KIF20A</i>, <i>ASPM</i>, <i>MELK</i>, and <i>NEK2</i>) were identified through network analysis. Among these, <i>MCM4</i> showed strong upregulation in LUAD and was significantly associated with poor overall survival. Notably, <i>MCM4</i> expression also correlated with post-progression survival and markers of invasiveness. Immunohistochemistry and transcriptomic analyses confirmed <i>MCM4</i> overexpression at both mRNA and protein levels. Additionally, <i>MCM4</i> expression was positively correlated with various matrix metalloproteinases, supporting its role in promoting tumor invasiveness. <b>Conclusions:</b> <i>MCM4</i> is a novel potential biomarker for LUAD metastasis and prognosis. Its consistent upregulation, association with metastatic markers, and clinical significance suggest it may serve as a candidate target for diagnostic use or therapeutic intervention in advanced LUAD.https://www.mdpi.com/2075-4418/15/12/1555lung adenocarcinomadifferentially expressed genesmetastasisMCM4 |
| spellingShingle | Hung-Chih Lai Ju-Fang Liu Tsung-Ming Chang Thai-Yen Ling MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma Diagnostics lung adenocarcinoma differentially expressed genes metastasis MCM4 |
| title | MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma |
| title_full | MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma |
| title_fullStr | MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma |
| title_full_unstemmed | MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma |
| title_short | MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma |
| title_sort | mcm4 as potential metastatic biomarker in lung adenocarcinoma |
| topic | lung adenocarcinoma differentially expressed genes metastasis MCM4 |
| url | https://www.mdpi.com/2075-4418/15/12/1555 |
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