Shandong University School of Medicine, Jinan, 250012, People's Republic of China.
J Neurooncol. 2012 Feb;106(3):543-9. doi: 10.1007/s11060-011-0710-6. Epub 2011 Oct 8.
High-mobility group A1 (HMGA1) protein is an architectural transcription factor widely expressed during embryonic development and tumor progression. The purpose of this research was to investigate the expression of HMGA1 in malignant gliomas with different WHO classification and to study the correlation of HMGA1 expression with tumor proliferation, invasion, and angiogenesis. Expression of HMGA1, Ki-67, MMP-9, VEGF-A, and MVD in malignant gliomas and their correlation were studied in 60 samples of different WHO classification by use of immunohistochemistry, and in 27 randomly selected samples by use of real-time quantitative PCR. Immunohistochemistry results showed that nuclear immunostaining of HMGA1 protein was not observed in normal brain tissues but was observed in 96.7% (58 of 60) of malignant gliomas including high (+++) in 15 (25.0%), moderate (++) in 28 (46.7%), and negligible to low (0-+) in 17 (28.3%) samples. Expression of HMGA1 protein was significantly higher in glioblastoma multiforme than in WHO grade II (P = 0.002) and WHO grade III gliomas (P = 0.024). HMGA1 protein expression correlated significantly with expression of Ki-67 (r = 0.530, P = 0.000), MMP-9 (r = 0.508, P = 0.000), VEGF-A (r = 0.316, P = 0.014), and MVD (r = 0.321, P = 0.012), but not with sex (r = 0.087, P = 0.510) and age (r = -0.121, P = 0.358). Real-time quantitative PCR results, also, were indicative of HMGA1 overexpression in glioblastoma multiforme compared with WHO grade II (P = 0.043) and WHO grade III (P = 0.031) gliomas. HMGA1 gene expression correlated significantly with gene expression of Ki-67 (r = 0.429, P = 0.025), MMP-9 (r = 0.443, P = 0.024), and VEGF-A (r = 0.409, P = 0.034). These results indicated that expression of HMGA1 correlates significantly with malignancy, proliferation, invasion, and angiogenesis of gliomas. We conclude that HMGA1 may be a potential biomarker and rational therapeutic target for human tumors.
高迁移率族蛋白 A1（HMGA1）蛋白是一种广泛表达于胚胎发育和肿瘤进展过程中的结构转录因子。本研究旨在探讨不同 WHO 分级的恶性胶质瘤中 HMGA1 的表达，并研究 HMGA1 表达与肿瘤增殖、侵袭和血管生成的相关性。采用免疫组织化学方法检测 60 例不同 WHO 分级的恶性胶质瘤组织中 HMGA1、Ki-67、MMP-9、VEGF-A 和 MVD 的表达，并采用实时定量 PCR 方法检测 27 例随机选择的样本。免疫组织化学结果显示，正常脑组织中未见 HMGA1 蛋白核免疫染色，而 60 例恶性胶质瘤中 96.7%（58/60）可见HMGA1 蛋白核免疫染色，其中高（+++）15 例（25.0%），中（++）28 例（46.7%），低至无（0-+）17 例（28.3%）。HMGA1 蛋白表达在多形性胶质母细胞瘤中明显高于 WHO Ⅱ级（P = 0.002）和 WHO Ⅲ级胶质瘤（P = 0.024）。HMGA1 蛋白表达与 Ki-67（r = 0.530，P = 0.000）、MMP-9（r = 0.508，P = 0.000）、VEGF-A（r = 0.316，P = 0.014）和 MVD（r = 0.321，P = 0.012）的表达显著相关，而与性别（r = 0.087，P = 0.510）和年龄（r = -0.121，P = 0.358）无关。实时定量 PCR 结果也显示，HMGA1 在多形性胶质母细胞瘤中的表达明显高于 WHO Ⅱ级（P = 0.043）和 WHO Ⅲ级（P = 0.031）胶质瘤。HMGA1 基因表达与 Ki-67（r = 0.429，P = 0.025）、MMP-9（r = 0.443，P = 0.024）和 VEGF-A（r = 0.409，P = 0.034）的基因表达显著相关。这些结果表明，HMGA1 的表达与胶质瘤的恶性程度、增殖、侵袭和血管生成密切相关。我们得出结论，HMGA1 可能是人类肿瘤的一个潜在的生物标志物和合理的治疗靶点。
