视网膜母细胞瘤高迁移率族蛋白A、MIB-1标记指数和let-7的表达及其相关性分析

Abstract

Objective To observe the expression and relationship of high-mobility group A(HMGA) 1,HMGA2,MIB-1 labeling index (LI) and let-7 in retinoblastoma (RB).Methods Forty-four RB samples were studied,including 11 poorly differentiated samples,33 well-differentiated samples; eight invasive and 36 non-invasive samples.The expression of HMGA1,HMGA2 and MIB-1 LI in RB were analyzed by immunohistochemitry.The HMGA1,HMGA2 were scored on a scale of 0 to high expression.0: no expression ; low: 1％ - 10 ％ ; medium: 11 ％ - 50 ％ ; high: ＞50 ％.The MIB LI were scored on a scale of 0to high expression.O: no expression;low: 1％ - 40％;high: ＞ 40％.Semiquantitative reverse transcription-polymerase chain reaction was used to assay the let-7 expression level: ≥ 80％ showed no significantly decreased expression; 60％ - 79％ showed medium decrease in expression; ＜ 60％ highly decreased in expression.Results In 44 RB samples,there were 14 cases with no HMGA1 expression (32％),11 cases with low expression (25％),10 cases with medium expression (23％),and nine cases with high expression (20％).Expression level of HMGA1 was significantly higher in poorly differentiated RB than in well-differentiated RB (x2 =11.3,P＜0.01) ; however,no statistically significant difference was found between invasive tumors and noninvasive tumors (x2 -5.9,P＞0.05).There were 11 cases with no HMGA2 expression (25％),11 cases with low expression-(25％),nine cases with medium expression (20％),and 13 cases with high expression (30％).Expression level of HMGA2 was significantly higher in poorly differentiated and invasive RB than in well differentiated and noninvasive RB respectively (x2=20.9,8.7; P＜0.05).There were 4 cases with no MIB-1 LI expression (9％),18 cases with low expression (41％),and 22 cases with high expression (50％).Expression level of MIB1 LI was significantly higher in poorly differentiated RB than in well-differentiated RB (t=5.2,P＜0.05).Higher expression of MIB-1 LI was found in invasive tumors than in noninvasive tumors,with no significant difference (t=-1.1,P＞0.05).Twenty seven cases had no significantly decreased expression of let-7 (61％).There were eight cases with medium decreased expression (18％) and nine cases with highly decreased expression (21％).Correlation analyses revealed that MIB1 LI expression significantly correlated with HMGA1and HMGA2 proteins (r=0.327,0.602; P＜0.05).A significantly inverse correlation existed between let-7 expression and HMGA1,HMGA2 proteins and MIB-1LI respectively (r=-0.247,-0.310,-0.392; P＜0.05).Conclusions Overexpression of HMGA1,HMGA2 and MIB-1 LI and down regulation of let-7 were demonstrated in RB.Supplying let-7 to RB cells can possibly inhibit HMGA1 and HMGA2 expression. Key words: Retinoblastoma/metabolism; Retinoblastoma protein; Tumor makers, biological; Genes, tumor suppressor