机构:[a]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[b]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China研究所北京市神经外科研究所首都医科大学附属天坛医院[c]Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China[d]Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China首都医科大学附属天坛医院[e]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China[f]China National Clinical Research Center for Neurological Diseases, Beijing, China
Background: PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Method and patients: Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis. Univariate and multivariate survival analysis were performed in 907 patients with survival data. Results: We found PD-1 was significantly upregulated in glioblastoma and isocitrate dehydrogenase wild type tumors. According to TCGA transcriptional classification scheme, PD-1 expression was higher in tumors of mesenchymal subtype than other subtypes, and shown good predictive value to mesenchymal subtype. GO analysis revealed that genes significantly correlated with PD-1 were involved in essential functions associated with anti-tumor immune process. Through screening transcriptomic data, we found a strong correlation between PD-1 and immune cell populations especially for T cells. In addition, we investigated the association between PD-1 and genes related to its function, and found that PD-1 was significantly correlated with genes including TGFB1, IDO1, CD40, ICOS and SATB1, and other immune checkpoint molecules including CTLA4, LAG3, TIM3 and CD276. Survival analysis suggested that higher PD-1 expression was independently associated with worse prognosis of patients with diffuse gliomas. Conclusion: Our results indicated that PD-1 was involved in key steps of anti-tumor immune process and independently predicted worse prognosis in diffuse gliomas. These findings may expend our understanding of potential anti-PD-1 treatments.
基金:
Capital Medical Development Research Fund [2016-2-1073, 2016-1-1072]; National Key Research and Development Plan [2016YFC0902500]; Beijing Postdoctoral Research FoundationChina Postdoctoral Science Foundation [2017-ZZ-116]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81502495, 81402052, 81702460, 81672479]; Beijing Science and Technology Plan [Z141100000214009]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [xxjh2015B063, Z171100001117022]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201708]
第一作者机构:[a]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[b]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
共同第一作者:
通讯作者:
通讯机构:[a]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[b]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[d]Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[e]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China[f]China National Clinical Research Center for Neurological Diseases, Beijing, China[*1]No.6, Tiantan Xili, Dongcheng District, Beijing, 100050, China.
推荐引用方式(GB/T 7714):
Shuai Liu,Zheng Wang,Yinyan Wang,et al.PD-1 related transcriptome profile and clinical outcome in diffuse gliomas[J].ONCOIMMUNOLOGY.2018,7(2):-.doi:10.1080/2162402X.2017.1382792.
APA:
Shuai Liu,Zheng Wang,Yinyan Wang,Xing Fan,Chuanbao Zhang...&Tao Jiang.(2018).PD-1 related transcriptome profile and clinical outcome in diffuse gliomas.ONCOIMMUNOLOGY,7,(2)
MLA:
Shuai Liu,et al."PD-1 related transcriptome profile and clinical outcome in diffuse gliomas".ONCOIMMUNOLOGY 7..2(2018):-