乙酰肝素酶mRNA在肝细胞癌中的表达及点突变研究

Heparanase mRNA expression and point mutation in hepatocellular carcinoma

目的探讨乙酰肝素酶(HPA)mRNA在肝细胞癌(HCC)中的表达及点突变的意义。方法应用逆转录聚合酶链反应(RTPCR)技术检测33例HCC中HPA的表达,用TA克隆测序法检测其扩增产物有无突变,并与HCC临床病理学指标分析。结果有16例癌组织HPA表达阳性,阳性率(48.5%)显著高于癌周肝组织(P<0.01)。术后转移复发组HPA阳性率显著高于无转移复发组(P<0.01)。7例PCR产物测序发现有4例均存在2处点突变,其中一处为有义突变,突变率为57.1%。结论HCC中HPAmRNA表达率增高,可作为HCC术后预测转移复发的一个重要指标。HPA基因点突变可能是其表达率增高的原因之一。

Objective To explore the expression of heparanase （HPA） mRNA and point mutation in hepatocellular carcinoma （HCC）, Methods Reverse transcription polymerase chain reaction （RT-PCR） was used to measure the HPA mRNA expression in the primary tumor tissues and surrounding liver tissues of 33 HCC patients, and T-A cloning and sequencing were used to detect whether there was mutation in the amplified PCR products. The results were statistically analyzed with clinical and pathological indexes. Results The HPA expression was positive in 16 primary tumor tissues of HCC, and the positive rate was 48,5 %, which was significantly higher than that in surrounding liver parenchyma （P〈0.01 ）, The positive rate for HPA gene in patients with postoperative metastatic recurrence was significantly higher than that in those without metastatic recurrence （P 〈 0.01 ）. Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 of 7 patients, one of which was sense mutation. Conclusion The expression rate of HPA mRNA in HCC is increased, and HPA mRNA may be one of the important markers to predict postoperative metastatic activity of HCC. Point mutation may be one of causes for enchanced HPA expression.