title: High leukocyte mitochondrial DNA content contributes to poor prognosis in glioma patients through its immunosuppressive effect.
abstract: BACKGROUND
  Epidemiological studies have indicated significant associations of leukocyte mitochondrial DNA (mtDNA) copy number with risk of several malignancies, including glioma. However, whether mtDNA content can predict the clinical outcome of glioma patients has not been investigated.
  
  
  METHODS
  The mtDNA content of peripheral blood leukocytes from 336 glioma patients was examined using a real-time PCR-based method. Kaplan-Meier curves and Cox proportional hazards regression model were used to examine the association of mtDNA content with overall survival (OS) and progression-free survival (PFS) of patients. To explore the potential mechanism, the immune phenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines from another 20 glioma patients were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.
  
  
  RESULTS
  Patients with high mtDNA content showed both poorer OS and PFS than those with low mtDNA content. Multivariate Cox regression analysis demonstrated that mtDNA content was an independent prognostic factor for both OS and PFS. Stratified analyses showed that high mtDNA content was significantly associated with poor prognosis of patients with younger age, high-grade glioma or adjuvant radiochemotherapy. Immunological analysis indicated that patients with high mtDNA content had significantly lower frequency of natural killer cells in PBMCs and higher plasma concentrations of interleukin-2 and tumour necrosis factor-α, suggesting an immunosuppression-related mechanism involved in mtDNA-mediated prognosis.
  
  
  CONCLUSIONS
  Our study for the first time demonstrated that leukocyte mtDNA content could serve as an independent prognostic marker and an indicator of immune functions in glioma patients.
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi'an, Shaanxi 710038, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi'an, Shaanxi 710038, China.
authors.forename: S
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: J
authors.initials: J
authors.lastname: Xing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001932:Brain Neoplasms / Q000097:blood / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D005910:Glioma / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial