{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:06:29Z","timestamp":1771927589073,"version":"3.50.1"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease (PD) is influenced by various factors, with lysosome function playing a critical role. However, the specific involvement of lysosome-related genes (LRGs) in PD remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to identify biomarkers specific to PD that exhibit robust disease prediction capabilities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Datasets for patients with PD, LRGs, and inflammation-related genes (IRGs) were retrieved from online databases. miRNAs and mRNAs within key modules were selected through Weighted Gene Co-expression Network Analysis (WGCNA), revealing strong associations with PD. A miRNA-mRNA network was constructed based on highly correlated PD-related LRGs (PD-LRGs) and miRNAs within these modules. Candidate genes were identified by intersecting target genes, differentially expressed genes (DEGs), PD-LRGs, and module-associated mRNAs. Machine learning and expression validation were employed to confirm these biomarkers. A nomogram was established, and its diagnostic performance was evaluated using a confusion matrix. Drug predictions were conducted based on these biomarkers. Spearman\u2019s correlation analyses were performed to assess the relationship between IRGs, freezing of gait (FOG)-related genes, and biomarkers. Molecular regulatory networks were constructed using datasets and online resources. Finally, clinical samples were collected for quantitative PCR (qPCR) validation of biomarker expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Key modules related to PD were identified, comprising 190 miRNAs and 7,633 mRNAs. A miRNA-mRNA network was constructed based on 55 PD-LRGs and 181 miRNAs, resulting in the identification of 26 candidate genes strongly linked to lysosomal function.\n                      <jats:italic>FGD4<\/jats:italic>\n                      and\n                      <jats:italic>MAN2B1<\/jats:italic>\n                      were selected as biomarkers, and a gene expression-based risk prediction table was created. These biomarkers were significantly correlated with IRGs and several FOG-related genes. Gene localization analysis revealed that\n                      <jats:italic>FGD4<\/jats:italic>\n                      and LRRK2, both critical to the FOG pathway, are located on chromosome 12. Drug prediction revealed that Tetrachlorodibenzodioxin and bisphenol A target both\n                      <jats:italic>FGD4<\/jats:italic>\n                      and\n                      <jats:italic>MAN2B1<\/jats:italic>\n                      . qPCR analysis confirmed that\n                      <jats:italic>FGD4<\/jats:italic>\n                      and\n                      <jats:italic>MAN2B1<\/jats:italic>\n                      expression levels were significantly higher in patients with PD compared to healthy controls (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>FGD4<\/jats:italic>\n                      and\n                      <jats:italic>MAN2B1<\/jats:italic>\n                      act as lysosomal biomarkers associated with PD and exhibit strong correlations with genes involved in PD-related freezing of gait. This study offers novel insights into PD diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1632163","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T01:55:33Z","timestamp":1769565333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA networks of lysosomal-related biomarkers in Parkinson\u2019s disease and their correlations with freezing of gait-associated genes"],"prefix":"10.3389","volume":"17","author":[{"given":"Zheng","family":"Qibin","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, National Regional Medical Center, The First Affiliated Hospital, Binhai Campus of the First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Department of Neurosurgery, Minnan Branch of The First Affiliated Hospital, Fujian Medical University","place":["Quanzhou, Fujian, China"]},{"name":"Fujian Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Yibiao","sequence":"additional","affiliation":[{"name":"Fujian Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]},{"name":"Department of Pain Management, First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pain Management, First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]},{"name":"Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Huiqing","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Regional Medical Center, The First Affiliated Hospital, Binhai Campus of the First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Fujian Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Daoqing","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Regional Medical Center, The First Affiliated Hospital, Binhai Campus of the First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Fujian Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]},{"name":"Neurosurgery Department of Shandong First Medical University Affiliated Central Hospital","place":["Jinan, China"]},{"name":"Center for Movement Disorders and Neuropathic Pain, BCI Patient Room, Xuanwu Jinan Hospital","place":["Jinan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Lianghong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Regional Medical Center, The First Affiliated Hospital, Binhai Campus of the First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Fujian Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108893","DOI":"10.1016\/j.isci.2024.108893","article-title":"Lysosomal stress drives the release of pathogenic \u03b1-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway","volume":"27","author":"Abe","year":"2024","journal-title":"iScience"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1111\/febs.12335","article-title":"The hallmarks of parkinson's disease","volume":"280","author":"Antony","year":"2013","journal-title":"Febs J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.parkreldis.2018.10.029","article-title":"The key role of T cells in parkinson's disease pathogenesis and therapy","volume":"60","author":"Baird","year":"2019","journal-title":"Park. 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