title: Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma.
abstract: The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p = 0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients.
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bou-Anak
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Burgett
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Nehaw
authors.initials: N
authors.lastname: Sarmey
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Khosla
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Dahiya
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA.
authors.forename: Eunnyung
authors.initials: E
authors.lastname: Bae
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: McGraw
authors.affiliation: Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Grove
authors.affiliation: Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Olman
authors.affiliation: Anatomic Pathology Laboratory, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Prayson
authors.affiliation: Radiation Oncology, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.affiliation: Quantitative Health Sciences, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Nowacki
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Barnett
authors.affiliation: The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA. gladsoc@ccf.org.|Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, NB40, Cleveland, OH, 44195, USA. gladsoc@ccf.org.
authors.forename: Candece L
authors.initials: CL
authors.lastname: Gladson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D005909:Glioblastoma / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: Age; Endothelial cell; Glioblastoma; Soluble TNF-R1; Soluble TNF-R2; Survival