title: ACTC1 as an invasion and prognosis marker in glioma.
abstract: OBJECTIVE Glioma is a major class of brain tumors, and glioblastoma (GBM) is the most aggressive and malignant type. The nature of tumor invasion makes surgical removal difficult, which results in remote recurrence. The present study focused on glioma invasion and investigated the expression of actin, alpha cardiac muscle 1 (ACTC1), which is 1 of 6 actin families implicated in cell motility. METHODS mRNA expression of ACTC1 expression was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in 47 formalin-fixed, paraffin-embedded glioma tissues that were graded according to WHO criteria: Grade I (n = 4); Grade II (n = 12); Grade III (n = 6); and Grade IV (n = 25). Survival was analyzed using the Kaplan-Meier method. The relationships between ACTC1 expression and clinical features such as radiological findings at the time of diagnosis and recurrence, patient age, Karnofsky Performance Scale status (KPS), and the MIB-1 index were evaluated. RESULTS The incidence of ACTC1 expression as a qualitative assessment gradually increased according to WHO grade. The hazard ratio for the median overall survival (mOS) of the patients with ACTC1-positive high-grade gliomas as compared with the ACTC1-negative group was 2.96 (95% CI, 1.03-8.56). The mOS was 6.28 years in the ACTC1-negative group and 1.26 years in the positive group (p = 0.037). In GBM patients, the hazard ratio for mOS in the ACTC1-positive GBMs as compared with the ACTC1-negative group was 2.86 (95% CI 0.97-8.45). mOS was 3.20 years for patients with ACTC1-negative GBMs and 1.08 years for patients with ACTC1-positive GBMs (p = 0.048). By the radiological findings, 42.9% of ACTC1-positive GBM patients demonstrated invasion toward the contralateral cerebral hemisphere at the time of diagnosis, although no invasion was observed in ACTC1-negative GBM patients (p = 0.013). The recurrence rate of GBM was 87.5% in the ACTC1-positive group; in contrast, none of the ACTC1-negative patients demonstrated distant recurrence (0.007). No remarkable relationship was demonstrated among ACTC1 expression and patient age, KPS, and the MIB-1 index. CONCLUSIONS ACTC1 may serve as a novel independent prognostic and invasion marker in GBM.
authors.affiliation: Departments of 1 Neurosurgery and.|Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Ohtaki
authors.affiliation: Departments of 1 Neurosurgery and.|Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Wanibuchi
authors.affiliation: Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kataoka-Sasaki
authors.affiliation: Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.|Department of Neurology, Yale University School of Medicine, New Haven; and.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Departments of 1 Neurosurgery and.|Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Noshiro
authors.affiliation: Departments of 1 Neurosurgery and.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Akiyama
authors.affiliation: Departments of 1 Neurosurgery and.|Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mikami
authors.affiliation: Departments of 1 Neurosurgery and.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Mikuni
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven; and.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Kocsis
authors.affiliation: Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.|Department of Neurology, Yale University School of Medicine, New Haven; and.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C526913:ACTC1 protein, human; D000199:Actins; D012333:RNA, Messenger
keywords: ACTC1; ACTC1 = actin, alpha cardiac muscle 1; CE-T1 = contrast-enhanced T1-weighted; CI = confidence interval; FFPE = formalin-fixed, paraffin-embedded; FLAIR = fluid-attenuated inversion recovery; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; GBM = glioblastoma; HGG = high-grade glioma; IDH = isocitrate dehydrogenase; KPS = Karnofsky Performance Scale; LGG = low-grade glioma; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; PFS = progression-free survival; astrocytoma; cytoskeletal filament; glioblastoma; high-grade glioma; invasion; mOS = median overall survival; mPFS = median progression-free survival; oncology; prognosis; qRT-PCR = quantitative real-time polymerase chain reaction