Gene-expression signature of vascular invasion in hepatocellular carcinoma.
Gene-expression signature of vascular invasion in hepatocellular carcinoma.
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DOI：
10.1016/j.jhep.2011.02.034
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发表时间：
2011-12
影响因子：
25.7
通讯作者：
Llovet, Josep M.
中科院分区：
文献类型：
--
作者：
Minguez, Beatriz;Hoshida, Yujin;Villanueva, Augusto;Toffanin, Sara;Cabellos, Laia;Thung, Swan;Mandeli, John;Sia, Daniela;April, Craig;Fan, Jian-Bing;Lachenmayer, Anja;Savic, Radoslav;Roayaie, Sasan;Mazzaferro, Vincenzo;Bruix, Jordi;Schwartz, Myron;Friedman, Scott L.;Llovet, Josep M.
关键词：
血管侵犯是肝细胞癌（HCC）手术治疗后肿瘤复发的主要预测因素。虽然肉眼可见的血管浸润可以通过放射学技术检测到，但术前检测显微镜下的血管浸润仍然很难，这使得30-40%的早期肿瘤患者变得复杂。共有214例接受切除术的肝细胞癌患者纳入本研究。通过使用79个丙型肝炎相关肝细胞癌样本（训练集）的全基因组基因表达谱，定义了与血管侵袭相关的基因表达特征。该签名在福尔马林固定的石蜡包埋组织中进行了验证，该组织来自一组独立的135名具有各种病因的患者。在训练集中定义了血管侵袭的35个基因签名，预测血管侵袭的准确率为69%。该特征与血管浸润（OR 3.38，95%CI 1.48-7.71，p = 0.003）沿着肿瘤大小（直径大于3 cm，OR 2.66，95%CI 1.17-6.05，p = 0.02）独立相关。在验证组中，特征丢弃了血管浸润的存在，阴性预测值为0.77，并且显著提高了单独肿瘤大小的诊断能力（p = 0.045）。对从切除的活检肿瘤标本中获得的基因表达特征的评估提高了血管浸润的诊断，超出了基于临床变量的预测。该特征可能有助于肝移植候选人的选择，并指导实验性辅助治疗的临床试验设计。
Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30–40% of patients with early tumors, remains elusive. A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48–7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17–6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.
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影响因子：
29.4
作者：
Roayaie S;Blume IN;Thung SN;Guido M;Fiel MI;Hiotis S;Labow DM;Llovet JM;Schwartz ME
通讯作者：
Schwartz ME
影响因子：
29.4
作者：
Llovet, Josep M.;Chen, Yingbei;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
7.5
作者：
Lim, SC
通讯作者：
Lim, SC
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR