2. Academic Validation
  3. Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes

Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes

  • EBioMedicine. 2022 Dec 14;87:104410. doi: 10.1016/j.ebiom.2022.104410.
Fan Wu 1,  Yi-Yun Yin 2,  Wen-Hua Fan 2,  You Zhai 2,  Ming-Chen Yu 2,  Di Wang 2,  Chang-Qing Pan 2,  Zheng Zhao 2,  Guan-Zhang Li 2,  Wei Zhang 3
Affiliations

Affiliations

  • 1 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, 100070, China. Electronic address: wufan0510284@163.com.
  • 2 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, 100070, China.
  • 3 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, 100070, China. Electronic address: zhangwei_vincent@126.com.
PMID: 36525723 DOI: 10.1016/j.ebiom.2022.104410
Abstract

Background: Human 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 by incomplete knowledge of somatic driving alterations and suboptimal disease classification. We herein aim to identify intrinsic molecular subtypes through integrated analysis of transcriptome, genome and methylome.

Methods: 137 oligodendroglioma patients from the Cancer Genome Atlas (TCGA) dataset were collected for unsupervised clustering analysis of immune gene expression profiles and comparative analysis of genome and methylome. Two independent datasets containing 218 patients were used for validation.

Findings: We identified and independently validated two reproducible subtypes associated with distinct molecular characteristics and clinical outcomes. The proliferative subtype, named Oligo1, was characterized by more tumors of CNS WHO grade 3, as well as worse prognosis compared to the Oligo2 subtype. Besides the clinicopathologic features, Oligo1 exhibited enrichment of cell proliferation, regulation of cell cycle and Wnt signaling pathways, and significantly altered genes, such as EGFR, NOTCH1 and MET. In contrast, Oligo2, with favorable outcome, presented increased activation of immune response and metabolic process. Higher T cell/APC co-inhibition and inhibitory checkpoint levels were observed in Oligo2 tumors. Finally, multivariable analysis revealed our classification was an independent prognostic factor in oligodendrogliomas, and the robustness of these molecular subgroups was verified in the validation cohorts.

Interpretation: This study provides further insights into patient stratification as well as presents opportunities for therapeutic development in human oligodendrogliomas.

Funding: The funders are listed in the Acknowledgement.

Keywords

Immunological profiling; Molecular subtype; Multi-omics; Oligodendrogliomas; Prognosis.

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