Your browser doesn't support javascript.
loading
Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas.
Ji, Hang; Liu, Zhihui; Wang, Nan; Jin, Jiaqi; Zhang, Jiheng; Dong, Jiawei; Wang, Fang; Yan, Xiuwei; Gong, Qin; Zhao, Hongtao; Sun, Haogeng; Li, Yongzhe; Hu, Shaoshan; You, Chao.
Afiliação
  • Ji H; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
  • Liu Z; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Wang N; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Jin J; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Zhang J; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Dong J; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Wang F; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Yan X; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Gong Q; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Zhao H; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Sun H; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Li Y; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
  • Hu S; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • You C; Cancer Center, Department of Neurosurgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Front Immunol ; 13: 970702, 2022.
Article em En | MEDLINE | ID: mdl-36159811
ABSTRACT
The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesis-related gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Front Immunol Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Front Immunol Ano de publicação: 2022 Tipo de documento: Article