title: Novel cancer-testis antigen expression on glioma cell lines derived from high-grade glioma patients.
abstract: Glioblastoma multiforme (GBM) is one of the most malignant and aggressive tumors, and has a very poor prognosis with a mean survival time of <2 years, despite intensive treatment using chemo-radiation. Therefore, novel therapeutic approaches including immunotherapy have been developed against GBM. For the purpose of identifying novel target antigens contributing to GBM treatment, we developed 17 primary glioma cell lines derived from high-grade glioma patients, and analyzed the expression of various tumor antigens and glioma-associated markers using a quantitative PCR and immunohistochemistry (IHC). A quantitative PCR using 54 cancer-testis (CT) antigen-specific primers showed that 36 CT antigens were positive in at least 1 of 17 serum-derived cell lines, and 17 antigens were positive in >50% cell lines. Impressively, 6 genes (BAGE, MAGE-A12, CASC5, CTAGE1, DDX43 and IL-13RA2) were detected in all cell lines. The expression of other 13 glioma-associated antigens than CT genes were also investigated, and 10 genes were detected in >70% cell lines. The expression of CT antigen and glioma-associated antigen genes with a high frequency were also verified in IHC analysis. Moreover, a relationship of antigen gene expressions with a high frequency to overall survival was investigated using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) database of the National Cancer Institute, and expression of 6 genes including IL-13RA2 was inversely correlated to overall survival time. Furthermore, 4 genes including DDX43, TDRD1, HER2 and gp100 were identified as MGMT-relevant factors. In the present study, several CT antigen including novel genes were detected in high-grade glioma primary cell lines, which might contribute to developing novel immunotherapy and glioma-specific biomarkers in future.
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Komiyama
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Yagoto
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ashizawa
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Oshita
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kume
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nogami
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ito
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Division of Pathology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugino
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mitsuya
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Nakamasa
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Division of Neurosurgery, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakasu
authors.affiliation: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor