{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:02Z","timestamp":1785404162749,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1R15CA287203"],"award-info":[{"award-number":["1R15CA287203"]}]},{"name":"NIH","award":["R16GM153522"],"award-info":[{"award-number":["R16GM153522"]}]},{"award":["1R15CA287203"],"award-info":[{"award-number":["1R15CA287203"]}],"id":[{"id":"https:\/\/ror.org\/05h1kgg64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R16GM153522"],"award-info":[{"award-number":["R16GM153522"]}],"id":[{"id":"https:\/\/ror.org\/05h1kgg64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background: Amyloid-related pathways are well studied in neurodegenerative diseases but remain poorly characterized in gliomas. Amyloid-related transcriptional programs in low-grade gliomas (astrocytoma grade II-III) and oligodendrogliomas, and their association with patient survival, were analyzed in this study. Methods: Transcriptomic data from 193 grade II-III astrocytomas and 191 oligodendrogliomas were analyzed to evaluate histology-specific expression patterns and prognostic significance. Differential and single-sample gene set enrichment analyses (ssGSEA) were used to calculate per-sample enrichment scores for 30 amyloid-related Gene Ontology biological process gene sets across the combined cohort. These scores were used to compare pathway activity between grade II-III astrocytoma and oligodendroglioma samples. Pathway-level survival analyses were performed for each tumor type using ssGSEA enrichment scores to evaluate associations with overall survival. Results: Distinct amyloid-related transcriptional programs were identified between glioma subtypes. Grade II-III astrocytomas showed enrichment of pathways related to amyloid precursor protein (APP) processing and amyloid-\u03b2 clearance, whereas oligodendrogliomas were enriched in lipid transport and negative regulation of amyloid formation. Survival analyses revealed that higher activity of the positive regulation of APP biosynthetic process and amyloid-\u03b2 clearance by transcytosis was significantly associated with worse overall survival in grade II-III astrocytoma, but not in oligodendroglioma. Gene-level analyses in astrocytoma demonstrated consistent survival associations across multiple genes within these pathways, supporting coordinated pathway-level effects rather than isolated single-gene prognostic markers. Conclusions: Amyloid-related transcriptional programs differ substantially between diffuse glioma subtypes. Increased APP biosynthesis and amyloid-\u03b2 transcytosis pathways are associated with poorer survival specifically in grade II-III astrocytoma, suggesting a potential role for amyloid metabolism in tumor progression. These findings identify APP-related pathways as candidates for further mechanistic investigation and potential therapeutic targeting in grade II-III astrocytoma.<\/jats:p>","DOI":"10.3390\/pathophysiology33020030","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytoma-Specific Prognostic Associations of Amyloid-Related Biological Processes"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5388-4327","authenticated-orcid":false,"given":"Felix Y.","family":"Narvaez Irizarry","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1413-2100","authenticated-orcid":false,"given":"Tyrel R.","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neisha","family":"Ramirez Serrano","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-5619","authenticated-orcid":false,"given":"Lilia Y.","family":"Kucheryavykh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0002-9440(10)61750-6","article-title":"Glioma Classification","volume":"159","author":"Louis","year":"2001","journal-title":"Am. 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