title: Circulating anti-filamin C autoantibody as a potential serum biomarker for low-grade gliomas.
abstract: BACKGROUND
  Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers.
  
  
  METHODS
  We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas.
  
  
  RESULTS
  FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients' sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC.
  
  
  CONCLUSIONS
  The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study.
authors.forename: Masayo
authors.initials: M
authors.lastname: Adachi-Hayama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Adachi
authors.forename: Natsuki
authors.initials: N
authors.lastname: Shinozaki
authors.forename: Tomoo
authors.initials: T
authors.lastname: Matsutani
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Naokatsu
authors.initials: N
authors.lastname: Saeki
authors.affiliation: Department of Neurological Surgery, Chiba University, Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. iwadatey@faculty.chiba-u.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D005260:Female; D064448:Filamins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000097:blood / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D064448:Filamins