Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes

• DOI: 10.1016/j.ebiom.2022.104410
• Publication Date: 2022-12-14T10:20:12Z
• Authors: Fan Wu; Yi-Yun Yin; Wen-Hua Fan; You Zhai; Ming-Chen Yu; Di Wang; Chang-Qing Pan; Zheng Zhao; Guan-Zhang Li; Wei Zhang
• Keywords: Chromosome Aberrations; 0301 basic medicine; Brain Neoplasms; Oligodendroglioma; Articles; Prognosis; Isocitrate Dehydrogenase; 3. Good health; 03 medical and health sciences; Chromosomes, Human, Pair 1; Mutation; Humans; Transcriptome

BackgroundHuman oligodendroglioma presents as a heterogeneous disease, primarily characterized by the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion. Therapy development for this tumor is hindered incomplete knowledge of somatic driving alterations suboptimal disease classification. We herein aim to identify intrinsic molecular subtypes through integrated analysis transcriptome, genome methylome.Methods137 patients from Cancer Genome Atlas (TCGA) dataset were collected unsupervised clustering immune gene expression profiles comparative methylome. Two independent datasets containing 218 used validation.FindingsWe identified independently validated two reproducible associated with distinct characteristics clinical outcomes. The proliferative subtype, named Oligo1, was more tumors CNS WHO grade 3, well worse prognosis compared Oligo2 subtype. Besides clinicopathologic features, Oligo1 exhibited enrichment cell proliferation, regulation cycle Wnt signaling pathways, significantly altered genes, such EGFR, NOTCH1 MET. In contrast, Oligo2, favorable outcome, presented increased activation response metabolic process. Higher T cell/APC co-inhibition inhibitory checkpoint levels observed in tumors. Finally, multivariable revealed our classification an prognostic factor oligodendrogliomas, robustness these subgroups verified validation cohorts.InterpretationThis study provides further insights into patient stratification opportunities therapeutic human oligodendrogliomas.FundingThe funders are listed Acknowledgement.