Departments of 1 Neurosurgery and.
Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
J Neurosurg. 2017 Feb;126(2):467-475. doi: 10.3171/2016.1.JNS152075. Epub 2016 Apr 15.
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.
目的
脑肿瘤主要包括胶质瘤，而胶质母细胞瘤（GBM）是最具侵袭性和恶性的类型。肿瘤侵袭的性质使得手术切除变得困难，这导致了远处复发。本研究专注于胶质瘤的侵袭，并研究了肌动蛋白、α 型心肌肌球蛋白 1（ACTC1）的表达，ACTC1 是涉及细胞运动的 6 种肌动蛋白家族之一。
方法
使用定量实时聚合酶链反应（qRT-PCR）分析 47 例福尔马林固定、石蜡包埋的脑肿瘤组织中 ACTC1 表达的 mRNA 表达，这些肿瘤根据世界卫生组织（WHO）标准分级：I 级（n = 4）；II 级（n = 12）；III 级（n = 6）；IV 级（n = 25）。使用 Kaplan-Meier 方法分析生存情况。评估 ACTC1 表达与放射学发现、诊断时和复发时的患者年龄、卡诺夫斯基表现状态（KPS）以及 MIB-1 指数等临床特征之间的关系。
结果
作为定性评估，ACTC1 表达的发生率根据 WHO 分级逐渐增加。与 ACTC1 阴性组相比，ACTC1 阳性高级别胶质瘤患者的中位总生存期（mOS）的风险比为 2.96（95%CI，1.03-8.56）。ACTC1 阴性组的 mOS 为 6.28 年，阳性组为 1.26 年（p = 0.037）。在 GBM 患者中，与 ACTC1 阴性 GBM 患者相比，ACTC1 阳性 GBM 患者的 mOS 风险比为 2.86（95%CI 0.97-8.45）。ACTC1 阴性 GBM 患者的 mOS 为 3.20 年，ACTC1 阳性 GBM 患者的 mOS 为 1.08 年（p = 0.048）。根据影像学发现，42.9%的 ACTC1 阳性 GBM 患者在诊断时表现出对侧大脑半球的侵袭，而 ACTC1 阴性 GBM 患者中没有观察到侵袭（p = 0.013）。ACTC1 阳性组 GBM 的复发率为 87.5%；相比之下，ACTC1 阴性组没有患者发生远处复发（0.007）。ACTC1 表达与患者年龄、KPS 和 MIB-1 指数之间没有明显的关系。
结论
ACTC1 可能是 GBM 中一种新的独立预后和侵袭标志物。
