{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:57:52Z","timestamp":1774342672782,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gliomas are the most common primary brain tumors and show marked molecular heterogeneity and variable clinical outcomes, highlighting the need for reliable prognostic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed TCGA and CGGA datasets to identify prognosis-related genes in glioma and performed single-cell analysis and functional validation in glioma cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten prognosis-related genes were identified, among which GLA showed the strongest association with survival. Elevated GLA expression was significantly associated with higher WHO grade, therapy resistance, and worse prognosis. Time-dependent ROC analysis showed favorable predictive performance for 1-, 3-, and 5-year survival. Single-cell RNA sequencing revealed preferential GLA expression in tumor-associated astrocytes and grade-dependent upregulation. GLA expression was associated with sphingolipid metabolism, hypoxia-related pathways, and ERAD-related pathways, including EDEM2 expression. In glioma cell lines, GLA knockdown suppressed cell viability and downregulated EDEM2. Cross-database analyses further supported the diagnostic and prognostic relevance of GLA across cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GLA may serve as a prognostic biomarker in glioma and is associated with metabolic and ERAD-related alterations, providing a potential direction for further mechanistic and therapeutic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1773193","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:25:15Z","timestamp":1774329915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sphingolipid metabolic enzyme GLA expression in gliomas: prognostic implications and therapeutic potential"],"prefix":"10.3389","volume":"16","author":[{"given":"Dan","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangkun","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina, Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology, the First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiong","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moujie","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, 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