The Loss Of Heterozygosity And Analysis Of ArgBP2 Deletion And Expression Involved In Hepatocellular Carcinoma

[Background and Objectives]Identification and characterization of loss of heterozygosity (LOH) can determine putative tumor suppressor genes (TSGs) and provide a variety of molecular markers for hepatocellular carcinoma (HCC). This study aimed to investigate LOH status on chromosomes 4q,6q,8p,9p and 17p and to explore their clinical significances in HCC post liver transplantation.[Methods] A total of thirty-seven patients with HCC who underwent liver transplantation were enrolled. LOH was examined using thirty-four microsatellite markers located on 4q13-q35,6q27,8p22-p23,9p21-p22 and 17p12-p13.[Results] The frequency of LOH at each microsatellite locus ranged from 23% to 75%, with a mean value of 53.1%. Frequencies of LOH on 4q,6q,8p,9p and 17p were 62%(23 of 37),30%(11 of 37),49%(18 of 37),46%(16 of 35), and 68% (25 of 37), respectively. LOHs on certain chromosomal regions were significantly associated with age, AFP level, tumor size, tumor multiplicity, histological grade, and metastatic recurrence.[Conclusions]LOH on 17p13.1 correlated to metastatic HCC recurrence, while LOH on 4q and 8p was found to be associated with progression of HCC. Thus, potential novel biomarkers or TSGs for prognosis and treatment of HCC may harbor on these regions. 【Baekground】We previously rePorted that the chromosome 4q35.l,on Whieh theArgBP2 gene exists,has frequent 1055 of heterozygosity(LOH)in hePatocellulareareinoma(HCC).This researeh aimed to validate LOH on the sPeeifie region ofchI0mosome4q and to measuxe the deletion and expression ofArgBP2.【Methods】Twenty-one mierosatellite markers were selected for LOH analysis onchromosome 4q in twenty-nine HCCs.mRNA eXPression of ArgBP2 gene wasinvestigated in HCC eell lines.We further examined the deletion and exPression ofArgBP2 in 42 HCCs and studied the elinicoPathologieal correlation with theexPreSSion of this gene.【Results】HighfrequencyofLOHoneaehmierosatelliteloeus(46.1%)wasobservedin HCCs.The locus D452920 with thehighest LOHfrequeney(11/19 HCCs,57.9%)could rePresent the Prefereniial deletion region 4q35.1,on whieh ArgBP2 and otherfour genes(ACSLI,CDKNZAIP,DCTD and ODZ3)were mapPed.LOH frequeney ofAigBP2 was 45.2%(14/31 HCCs).The mRNA exPressionofthisgenewasredueedinHCC eell lines and was signifieantly lower in tumor tissues than in eorresPondingnon-tumor tissues(P=0.0106)in HCCs.Consistently,the exPression ofAigBPZ inHCC tissues was decreased or even lost at Protein level.Moreover,we found that themRNA exPression ofAigBPZ was down-regulated more frequently in tumors with sizeno more than 5 cm(P-0.0201).【Conelusion】AigBp2 might play a role in HCC as a tumors即pressor gene.LOH 15likely to be a critieal,but not the unique meehanism for AigBPZ reduced exPression...