title: HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis.
abstract: 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.
authors: Shandong University School of Medicine, Jinan, 250012, People's Republic of China.
authors: Bo
authors: B
authors: Pang
authors: Haitao
authors: H
authors: Fan
authors: Ian Y
authors: IY
authors: Zhang
authors: Bin
authors: B
authors: Liu
authors: Bin
authors: B
authors: Feng
authors: Lei
authors: L
authors: Meng
authors: Rui
authors: R
authors: Zhang
authors: Sam
authors: S
authors: Sadeghi
authors: Hua
authors: H
authors: Guo
authors: Qi
authors: Q
authors: Pang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000150:complications / Q000378:metabolism / Q000473:pathology; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000209:etiology*; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D025741:HMGA1a Protein; D020780:Matrix Metalloproteinase 9