目的:检测高迁移率蛋白A2(high mobility group A2,HMGA2)、let-7家族microRNA和P53在浆液性卵巢癌中的表达,分析HMGA2和let-7家族microRNA的关系,比较HMGA2与P53在浆液性卵巢癌中的表达情况。方法:用免疫组织化学方法检测50例卵巢癌和4例正常输卵管石蜡包埋标本中HMGA2和P53蛋白的表达,采用实时荧光定量逆转录-PCR方法检测对应标本以及卵巢癌细胞系中HMGA2 mRNA和let-7家族microRNA的表达。结果:HMGA2和P53在浆液性卵巢癌中免疫组织化学染色阳性率分别为70%(35/50)和78%(39/50)。HMGA2在输卵管纤毛上皮中有微弱表达,在分泌型上皮细胞中不表达;HMGA2的表达存在随着肿瘤病理分级的增高而增高的趋势,但与肿瘤临床分期没有关系。HMGA2 mRNA在所有卵巢癌标本中均能检测到,但在72%(36/50)的标本中表达量高于正常输卵管组;恶性程度高的细胞系(SKOV3.ipl)比恶性程度低(SKOV3)的细胞系HMGA2 mRNA表达更高。let-7家族各成员在所有浆液性卵巢癌标本中均表达,其表达量与HMGA2 mRNA呈低度负相关(r=-0.305,P〈0.05)。结论:HMGA2可能与P53一样,可以作为浆液性卵巢癌的生物标志物,其表达与浆液性卵巢癌恶性程度有关。let-7表达降低是HMGA2在浆液性卵巢癌中高表达的一种、但非唯一机制。
Objective:To examine the expression of high mobility group A2(HMGA2),P53 and let-7 family microRNA,to investigate the correlation of HMGA2 and let-7,and to compare the HMGA2 and P53 expressions in human serous ovarian cancer.Methods: Immunohistochemistry assay was used to examine the expressions of HMGA2 and P53 in 50 paraffin-embedded tissue specimens of human serous ovarian cancer and 4 normal fallopian tube tissues.HMGA2 mRNA and let-7 family microRNA were detected by real time fluorescent quantitative reverse transcription polymerase chain reaction in the corresponding frozen tissues.Results: HMGA2 and P53 were immuno-positive in 70%(35/50) and 78%(39/50) of the ovarian cancer tissues,respectively.HMGA2 was weakly expressed in the ciliated cells,but negative in the secretary cells of the fallopian tube.There was a tendency that the expression of HMGA2 increased with higher pathological grade of the ovarian cancer,but no correlation was observed between the HMGA2 overexpression and clinical stages.HMGA2 mRNA was detected in all the ovarian cancer samples,and its expression level was higher than that of the normal fallopian tube tissues in 72%(36/50)of the ovarian cancer samples.The expression of HMGA2 mRNA was much higher in more malignant SKOV3.ipl cells than in its corresponding SKOV3 cells.All let-7 family members were detectable in all ovarian cancer samples,and their expression were inversely correlated with HMGA2 mRNA expression(r=-0.305,P0.05).Conclusion: HMGA2 can be a biomarker complement to P53,and its high expression has an inclination of more malignancy.The downregulation of let-7 is,but not the only mechanism of HMGA2 overexpression in serous ovarian cancer.