RIT1基因在肝细胞癌中的扩增及其临床意义

Amplification of RIT1 in Hepatocell ular Carcinoma and Its Clinical Significance

背景与目的:已有的研究显示肝细胞癌的染色体1q有高频扩增,1q21-22是最小的高频扩增区带之一,可能存在肝细胞癌相关的候选癌基因。RIT1基因位于1q21.3区带,是Ras的亚家族成员,RIT1蛋白在分子结构和功能方面与Ras蛋白非常相似,推测RIT1基因可能是肝细胞癌的候选癌基因之一。因此,本研究通过检测肝细胞癌RIT1基因的扩增情况,并与临床指标相联系,探讨该基因对肝细胞癌发生和发展的可能作用。方法:建立荧光定量PCR的方法,在PEABI7000型荧光定量PCR仪上检测43例肝细胞癌患者手术切除的癌组织及远癌肝组织RIT1基因的拷贝数,并用癌组织与癌旁肝组织基因拷贝数的比值作为RIT1基因的扩增倍数。结果:在43例肝细胞癌患者中,11例有RIT1基因的扩增,扩增率为25.6%;将基因扩增组与非扩增组比较,基因扩增组的生存期(平均15个月)明显短于非扩增组(平均34个月),P=0.0009,且在病理分级和肝硬化程度方面也具有明显的差异,P<0.01。结论:基因扩增可能是癌基因RIT1在肝细胞癌的激活方式之一,该基因的扩增可能对肝细胞癌的发生发展起一定的作用。

BACKGROUND &OBJECTIVE:Previous study has demonstrated that hig h frequent g ain of 1q was dete cted in hepatocellular carcinoma (HCC),1q21-22was identified as the minimu m overlapping amplified reg ion and m ig ht contain the candidate oncog enes involved in HCC.RIT1g ene is located in1q21·3reg ion and is a member of Ras subfami ly.RIT1protein is similar to Ras protein in molecular structure and f unctions.It was speculated that RIT1g ene mig ht be a candidate oncog ene in HCC.So,the amplification of RIT1g ene wa s examined in HCC and was linked with th e clinical indicators in this study t o explore the possible functions of RI T1g ene in HCC development and prog ression.METHODS :The fluorescence quantitative poly merase chain reaction(FQ-PCR)method was established successfull y.The number of RIT1g ene DNA copies was examined in the tu mor tissues and its paratumor tissues from 43patients with HCC by PE ABI 7000Sequence Detector.The ratio of the number of RIT1g ene DNA copies between the tumor tissue and its paratumor tissue represented the extent of amp lification of RIT1g ene DNA.RESULTS :RIT1g ene DNA was amplified in 11case s(25.6%)among 43patients.The mean survival time (15months )of the RIT1g ene-amplification g rou p is sig nificantly shorter than that (34months )of the non-amplification g roup(P=0.0009);furthermore,the patholog ical g ra de and the extent of liver cirrhosis were sig nificantly different betwe en the RIT1g ene-amplification g roup and the non-amplification g roup(P<0.01).CONCLUSION:The amplification of RIT1g ene mig ht be one of the activation wa ys in HCC and mig ht play an important r ole in HCC development and prog ression.