中华肝胆外科杂志
中華肝膽外科雜誌
중화간담외과잡지
CHINESE JOURNAL OF HEPATOBILIARY SURGERY
2015年
7期
458-461
,共4页
逄锦忠%焦学飞%王光军%钦伦秀%任宁%叶青海%刘银坤%汤钊猷
逄錦忠%焦學飛%王光軍%欽倫秀%任寧%葉青海%劉銀坤%湯釗猷
방금충%초학비%왕광군%흠륜수%임저%협청해%류은곤%탕쇠유
肝细胞癌%TNM Ⅰ期%杂合性缺失%分子分期%预后
肝細胞癌%TNM Ⅰ期%雜閤性缺失%分子分期%預後
간세포암%TNM Ⅰ기%잡합성결실%분자분기%예후
Hepatocellular carcinoma%TNM stage Ⅰ%Loss of heterozygosity%Molecular staging%Prognosis
目的 探讨染色体杂合性缺失(LOH)在TNM Ⅰ期肝细胞癌(HCC)分子分期预后评估中的价值.方法 对1999年1月至2000年3月131例行根治术的TNM Ⅰ期HCC石蜡标本应用微切割技术,获取纯净肿瘤DNA进行LOH检测.选取1p、8p、17p、4q、13q及16q 6条染色体上24个具有高度多态性的微卫星标记.分析LOH与TNM Ⅰ期HCC患者根治术后5年总体生存(OS)、无瘤生存(DFS)的关系.结果 LOH在检测的染色体位点上发生明显,D8S298位点、D1S199位点LOH频率分别为31.5％、33.7％.在单因素分析中,D8S298位点LOH的患者根治术后5年OS、DFS率皆明显低于无LOH的患者(46 ±5比62 ±2,P＜0.05;44 ±5比57 ±3,P＜0.05).同样,在D1S199基因位点,LOH患者术后5年OS、DFS率亦显著低于无LOH者(42 ±4比61 ±2,P＜0.05;41 ±5比57 ±3,P＜0.05).在多因素分析中,Cox比例风险模型显示D8S298位点LOH是TNM Ⅰ期HCC患者根治术后DFS较差的独立因素(HR=0.372;95％ CI=0.146～0.948;P＜0.05),而D1S199位点LOH是TNM Ⅰ期HCC患者根治术后OS较差的独立因素(HR =0.281;95％ CI=0.123 ～0.643;P ＜0.05).结论 D8S298、D1S199位点LOH可以作为TNM Ⅰ期HCC根治术后新型的预后预测分子标记,对TNM Ⅰ期HCC的分子分期具有重要价值.
目的 探討染色體雜閤性缺失(LOH)在TNM Ⅰ期肝細胞癌(HCC)分子分期預後評估中的價值.方法 對1999年1月至2000年3月131例行根治術的TNM Ⅰ期HCC石蠟標本應用微切割技術,穫取純淨腫瘤DNA進行LOH檢測.選取1p、8p、17p、4q、13q及16q 6條染色體上24箇具有高度多態性的微衛星標記.分析LOH與TNM Ⅰ期HCC患者根治術後5年總體生存(OS)、無瘤生存(DFS)的關繫.結果 LOH在檢測的染色體位點上髮生明顯,D8S298位點、D1S199位點LOH頻率分彆為31.5％、33.7％.在單因素分析中,D8S298位點LOH的患者根治術後5年OS、DFS率皆明顯低于無LOH的患者(46 ±5比62 ±2,P＜0.05;44 ±5比57 ±3,P＜0.05).同樣,在D1S199基因位點,LOH患者術後5年OS、DFS率亦顯著低于無LOH者(42 ±4比61 ±2,P＜0.05;41 ±5比57 ±3,P＜0.05).在多因素分析中,Cox比例風險模型顯示D8S298位點LOH是TNM Ⅰ期HCC患者根治術後DFS較差的獨立因素(HR=0.372;95％ CI=0.146～0.948;P＜0.05),而D1S199位點LOH是TNM Ⅰ期HCC患者根治術後OS較差的獨立因素(HR =0.281;95％ CI=0.123 ～0.643;P ＜0.05).結論 D8S298、D1S199位點LOH可以作為TNM Ⅰ期HCC根治術後新型的預後預測分子標記,對TNM Ⅰ期HCC的分子分期具有重要價值.
목적 탐토염색체잡합성결실(LOH)재TNM Ⅰ기간세포암(HCC)분자분기예후평고중적개치.방법 대1999년1월지2000년3월131례행근치술적TNM Ⅰ기HCC석사표본응용미절할기술,획취순정종류DNA진행LOH검측.선취1p、8p、17p、4q、13q급16q 6조염색체상24개구유고도다태성적미위성표기.분석LOH여TNM Ⅰ기HCC환자근치술후5년총체생존(OS)、무류생존(DFS)적관계.결과 LOH재검측적염색체위점상발생명현,D8S298위점、D1S199위점LOH빈솔분별위31.5％、33.7％.재단인소분석중,D8S298위점LOH적환자근치술후5년OS、DFS솔개명현저우무LOH적환자(46 ±5비62 ±2,P＜0.05;44 ±5비57 ±3,P＜0.05).동양,재D1S199기인위점,LOH환자술후5년OS、DFS솔역현저저우무LOH자(42 ±4비61 ±2,P＜0.05;41 ±5비57 ±3,P＜0.05).재다인소분석중,Cox비례풍험모형현시D8S298위점LOH시TNM Ⅰ기HCC환자근치술후DFS교차적독립인소(HR=0.372;95％ CI=0.146～0.948;P＜0.05),이D1S199위점LOH시TNM Ⅰ기HCC환자근치술후OS교차적독립인소(HR =0.281;95％ CI=0.123 ～0.643;P ＜0.05).결론 D8S298、D1S199위점LOH가이작위TNM Ⅰ기HCC근치술후신형적예후예측분자표기,대TNM Ⅰ기HCC적분자분기구유중요개치.
Objective To explore the prognostic value of chromosomal loss of heterozygosity (LOH) in molecular staging for tumor-node-metastasis (TNM) stage Ⅰ of hepatocellular carcinoma (HCC) using survival analysis.Methods 131 patients with TNM stage Ⅰ of HCC who underwent curative liver resection from January 1999 to March 2000 were enrolled.Genomic DNA was extracted from the microdissected HCC paraffin-embedded tissue samples for LOH detection using 24 high-polymorphic microsatellite markers located at chromosomes 1p,8p,17p,4q,13q,and 16q,and its associations with the 5-year overall survival (OS) and the disease-free survival (DFS) of these patients were analyzed.Results LOH was frequent at the chromosomal loci analyzed.The LOH frequencies at D8S298 and D1S199 were 31.5％ and 33.7％,respectively.On univariate analysis,D8S298 LOH in the entire cohort was associated with a significantly worse 5-year OS (46 ± 5 vs.62 ± 2,P ＜ 0.05) and DFS (44 ± 5 vs.57 ± 3,P ＜ 0.05).Likewise,patients with D1 S199 LOH had significantly worse 5-year OS (42 ± 4 vs.61 ± 2,P ＜ 0.05) and DFS (41 ± 5 vs.57 ±3,P ＜ 0.05) than those without.On multivariate analyses,LOH at D8S298 was an independent predictor of decreased DFS (HR =0.372;95％ CI=0.146 ～0.948;P ＜0.05),whereas LOH at D1S199 was an independent predictor of decreased OS (HR =0.281;95％ CI =0.123 ～ 0.643;P ＜ 0.05).Conclusion LOH at D8S298 and D1S199 could serve as novel biomarkers of prognostic prediction for patients with TNM stage Ⅰ of HCC after curative liver resection,and it would be of great value in molecular staging for TNM stage Ⅰ of HCC.
