Department of Oral Pathology, Oral Cancer Research Institute, Seoul, Republic of Korea.
Division of Anatomy and Developmental Biology, Department of Oral Biology, Seoul, Republic of Korea.
Oral Dis. 2019 May;25(4):1158-1168. doi: 10.1111/odi.13070. Epub 2019 Mar 15.
Ameloblastomas are the most common odontogenic epithelial tumors with high recurrence rate. The aim of this study was to identify apoptosis-related genes with recurrence of ameloblastomas and to evaluate its feasibility as a prognostic marker and as a target molecule preventing from recurrence.
Public microarray data were analyzed. To evaluate their expression in ameloblastoma patients, immunohistochemical staining was performed in 89 human ameloblastoma tissues. Quantitative PCR was performed by use of ameloblastoma cell line (AM-1). Fluorescence activated cell sorting analysis and western blotting were conducted following transfection with siRNA. Further, AM-1 cells were implanted in the renal subcapsular layer of immunodeficient mice.
Microarray data analysis revealed that osteoprotegerin (OPG) and B-cell lymphoma 2 (Bcl-2) were the two most upregulated genes in ameloblastoma. Only Bcl-2 expression was significantly (p = 0.020) associated with recurrence in conservative treatment group (n = 17) among 89 patients. Silencing of Bcl-2 increased apoptosis in AM-1 cells in vitro and inhibited tumor nodule formation of AM-1 cells in vivo.
These results suggest that Bcl-2 expression is a useful biomarker to predict recurrence of ameloblastomas, and as a therapeutic target molecule to prevent recurrence of ameloblastoma.
成釉细胞瘤是最常见的牙源性上皮性肿瘤，具有较高的复发率。本研究旨在鉴定与成釉细胞瘤复发相关的凋亡相关基因，并评估其作为预后标志物和预防复发的靶向分子的可行性。
分析公共微阵列数据。为了评估它们在成釉细胞瘤患者中的表达，对 89 个人类成釉细胞瘤组织进行了免疫组织化学染色。使用成釉细胞瘤细胞系（AM-1）进行定量 PCR。转染 siRNA 后进行荧光激活细胞分选分析和 Western blot。进一步将 AM-1 细胞植入免疫缺陷小鼠的肾被膜下。
微阵列数据分析显示，骨保护素（OPG）和 B 细胞淋巴瘤 2（Bcl-2）是成釉细胞瘤中上调最明显的两个基因。在 89 名患者中，只有在保守治疗组（n=17）中，Bcl-2 的表达与复发显著相关（p=0.020）。体外沉默 Bcl-2 可增加 AM-1 细胞的凋亡，并抑制 AM-1 细胞体内肿瘤结节的形成。
这些结果表明，Bcl-2 的表达是预测成釉细胞瘤复发的有用生物标志物，也是预防成釉细胞瘤复发的治疗靶点分子。
