title: Identification of a 6-cytokine prognostic signature in patients with primary glioblastoma harboring M2 microglia/macrophage phenotype relevance.
abstract: BACKGROUND
  Glioblastomas (GBM) are comprised of a heterogeneous population of tumor cells, immune cells, and extracellular matrix. Interactions among these different cell types and pro-/anti-inflammatory cytokines may promote tumor development and progression.
  
  
  OBJECTIVE
  The objective of this study was to develop a cytokine-related gene signature to improve outcome prediction for patients with primary GBM.
  
  
  METHODS
  Here, we used Cox regression and risk-score analysis to develop a cytokine-related gene signature in primary GBMs from the whole transcriptome sequencing profile of the Chinese Glioma Genome Atlas (CGGA) database (n=105). We also examined differences in immune cell phenotype and immune factor expression between the high-risk and low-risk groups.
  
  
  RESULTS
  Cytokine-related genes were ranked based on their ability to predict survival in the CGGA database. The six genes showing the strongest predictive value were CXCL10, IL17R, CCR2, IL17B, IL10RB, and CCL2. Patients with a high-risk score had poor overall survival and progression-free survival. Additionally, the high-risk group was characterized by increased mRNA expression of M2 microglia/macrophage markers and elevated levels of IL10 and TGFβ1.
  
  
  CONCLUSIONS
  The six cytokine-related gene signature is sufficient to predict survival and to identify a subgroup of primary GBM exhibiting the M2 cell phenotype.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jinchong
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics; D054357:Chemokine CXCL10 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D019175:DNA Methylation; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D008264:Macrophages / Q000473:pathology*; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D054390:Receptors, CCR2 / Q000235:genetics; D053722:Receptors, Interleukin-17 / Q000235:genetics; D012307:Risk Factors; D016019:Survival Analysis; D059467:Transcriptome; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D016207:Cytokines; C081846:IL10RB protein, human; C515924:IL17B protein, human; C109985:IL17RA protein, human; D053710:Interleukin-10 Receptor beta Subunit; D020381:Interleukin-17; D054390:Receptors, CCR2; D053722:Receptors, Interleukin-17