Classification of diffuse lower‐grade glioma based on immunological profiling
| العنوان: | Classification of diffuse lower‐grade glioma based on immunological profiling |
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| المؤلفون: | Haoyu Jiang, Yu-Qing Liu, Wei Zhang, Yuemei Feng, Fan Wu, Guanzhang Li, Kuanyu Wang, You Zhai, Zheng Zhao, Rui-Chao Chai, Zhiliang Wang |
| المصدر: | Molecular Oncology, Vol 14, Iss 9, Pp 2081-2095 (2020) Molecular Oncology |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Cancer Research, Lymphocyte, medicine.medical_treatment, Biology, lcsh:RC254-282, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Lymphocytes, Tumor-Infiltrating, Glioma, Genetics, medicine, Cluster Analysis, Humans, tumor microenvironment, Research Articles, Proportional Hazards Models, Tumor microenvironment, Brain Neoplasms, Genome, Human, Reproducibility of Results, General Medicine, Immunotherapy, T helper cell, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, diffuse lower‐grade glioma, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Female, prognosis, Neoplasm Grading, CD8, immune classification, Research Article |
| الوصف: | Transcriptomic data derived from bulk sequencing have been applied to delineate the tumor microenvironment (TME) and define immune subtypes in various cancers, which may facilitate the design of immunotherapy treatment strategies. We herein gathered published gene expression data from diffuse lower‐grade glioma (LGG) patients to identify immune subtypes. Based on the immune gene profiles of 402 LGG patients from The Cancer Genome Atlas, we performed consensus clustering to determine robust clusters of patients, and evaluated their reproducibility in three Chinese Glioma Genome Atlas cohorts. We further integrated immunogenomics methods to characterize the immune environment of each subtype. Our analysis identified and validated three immune subtypes—Im1, Im2, and Im3—characterized by differences in lymphocyte signatures, somatic DNA alterations, and clinical outcomes. Im1 had a higher infiltration of CD8+ T cells, Th17, and mast cells. Im2 was defined by elevated cytolytic activity, exhausted CD8+ T cells, macrophages, higher levels of aneuploidy, and tumor mutation burden, and these patients had worst outcome. Im3 displayed more prominent T helper cell and APC coinhibition signatures, with elevated pDCs and macrophages. Each subtype was associated with distinct somatic alterations. Moreover, we applied graph structure learning‐based dimensionality reduction to the immune landscape and revealed significant intracluster heterogeneity with Im2 subtype. Finally, we developed and validated an immune signature with better performance of prognosis prediction. Our results demonstrated the immunological heterogeneity within diffuse LGG and provided valuable stratification for the design of future immunotherapy. We classified diffuse lower‐grade gliomas (LGGs) into three distinct subtypes based on consensus clustering of immune‐related gene expression profiles. Each of the three immune subtypes was associated with distinct molecular and cellular features, and clinical outcomes. The identification of immune‐related subtypes may facilitate the optimal selection of LGG patients responsive to immunotherapy. |
| اللغة: | English |
| تدمد: | 1574-7891 1878-0261 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62bfe5cb58c82ace8b27c342600ca4cdTest https://doaj.org/article/238a5db78908445a9967a767b7c5a9e8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62bfe5cb58c82ace8b27c342600ca4cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15747891 18780261 |
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