CAJ | 학술논문

目的研究4号染色体长臂(4q)拷贝数变异(CNA)与肝细胞癌(HCC)术后复发的相关性,并探讨复发表征基因.方法纳入179例HCC,其中66例有术后复发随访资料.采用微阵列比较基因组杂交和表达芯片分别检测CNA和基因mRNA表达差异;CNA与复发相关性分析采用生存分析;癌与配对癌旁肝组织间拷贝数相关性采用Spearman检验;基因表达水平的组间比较采用Mann-Whitney U检验.结果片段性或全臂4q丢失发生率为63.6％ (42/66).生存分析显示,8个非纯合丢失片段与HCC复发无关(P＞0.05);而4q13.2纯合缺失是HCC复发的独立预后因素[风险比(HR)=2.26,95％可信区间(CI) =1.13 ～4.50,P＜0.05].癌和配对癌旁肝组织的4q13.2拷贝数具有一致性(r =0.868,P ＜0.05).定位4q13.2基因的CNA与表达联合分析显示,基因纯合缺失HCC的UGT2B17表达水平较非纯合缺失HCC及癌旁肝组织显著降低(P＜0.05);UGT2B17表达阴性HCC的血管侵犯发生率显著高于表达阳性者(P＜0.05).结论遗传性4q13.2纯合缺失是HCC术后复发的独立预后因素,UGT2B17可能是该复发相关片段的表征基因.
목적 연구4호염색체장비(4q)고패수변이(CNA)여간세포암(HCC)술후복발적상관성,병탐토복발표정기인.방법 납입179례HCC,기중66례유술후복발수방자료.채용미진렬비교기인조잡교화표체심편분별검측CNA화기인mRNA표체차이;CNA여복발상관성분석채용생존분석;암여배대암방간조직간고패수상관성채용Spearman검험;기인표체수평적조간비교채용Mann-Whitney U검험.결과 편단성혹전비4q주실발생솔위63.6％ (42/66).생존분석현시,8개비순합주실편단여HCC복발무관(P＞0.05);이4q13.2순합결실시HCC복발적독립예후인소[풍험비(HR)=2.26,95％가신구간(CI) =1.13 ～4.50,P＜0.05].암화배대암방간조직적4q13.2고패수구유일치성(r =0.868,P ＜0.05).정위4q13.2기인적CNA여표체연합분석현시,기인순합결실HCC적UGT2B17표체수평교비순합결실HCC급암방간조직현저강저(P＜0.05);UGT2B17표체음성HCC적혈관침범발생솔현저고우표체양성자(P＜0.05).결론 유전성4q13.2순합결실시HCC술후복발적독립예후인소,UGT2B17가능시해복발상관편단적표정기인.
Objective To investigate the association between copy numbealteration(CNAs) in chromosome 4 long arm (4q) and postoperative recurrence of hepatocellulacarcinom(HCC), and furthescreen fothe possible phenotypigene (s) in the potentially recurrence-related CN(s) in 4q.Methodtotal of 179 HCcasewere enrolled, including 66 patientfowhom follow-up datof postoperative recurrence are available.Array comparative genomihybridization and expression arraywere used to detecCNAand gene mRNexpression levels, respectively.The associationbetween 4q CNAand postoperative recurrence were analyzed using Log-rank test, Kaplan-Meiesurvival analysiand Cox proportional hazardmodels.The correlation of the copy numberin HCand matched non-tumolivetissue waassessed using Spearman' test.The gene expression levelbetween HCCwith gene homozygoudeletion, HCCwithout, and non-tumolivetissuewere compared by Maan-Whitney U test.ResultRegional owhole chromosome arm losof 4q wadetected in 42 of the 66 case(63.6％).Survival analysishowed thahomozygoudeletion a4q13.2, bunone of the 8 non-homozygoulosses, waan independenprognostifactoforecurrence [hazard ratio (HR) =2.26, 95％ confidence interval (CI) =1.13-4.50, P ＜0.05].Comparative analysishowed tha4q13.2 copy numberin HCCand matched non-tumolivetissue were highly correlated (=0.868, P ＜ 0.05).Integration analysiof CNand expression datshowed thathe expression level of gene UGT2B17, mapping a4q13.2, wasignificantly decreased in HCCwith homozygoudeletion when compared with HCCwithouhomozygoudeletion owith non-tumolivetissue(both P ＜ 0.05).Vasculainvasion wamore frequently found in HCCwith negative UGT2B17 expression than thawith positive expression (P ＜ 0.05).Conclusion Germline homozygoudeletion on 4q13.2 ian independenprognostimarkefopostoperative recurrence fopatientwith HCC, and UGT2B17 ithe probable phenotypigene of the 4q13.2 homozygoudeletion.