Molecular Scoring of Hepatocellular Carcinoma for Predicting Metastatic Recurrence and Requirements of Systemic Chemotherapy.
Molecular Scoring of Hepatocellular Carcinoma for Predicting Metastatic Recurrence and Requirements of Systemic Chemotherapy.
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DOI：
10.3390/cancers10100367
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发表时间：
2018-09-29
期刊：
影响因子：
5.2
通讯作者：
Kudo M
中科院分区：
文献类型：
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作者：
Nishida N;Nishimura T;Kaido T;Minaga K;Yamao K;Kamata K;Takenaka M;Ida H;Hagiwara S;Minami Y;Sakurai T;Watanabe T;Kudo M
肝细胞癌 (HCC) 是最常见的癌症相关死亡之一； HCC 亚型显示出影响生存的快速进展。我们阐明了侵袭性 HCC 的分子特征，并建立了预测治愈性治疗后转移的分子评分系统。总共检查了 125 个 HCC 的 TP53、CTNNB1 和 TERT 启动子突变、8 个肿瘤抑制基因的甲基化和 3 个重复 DNA 序列，以估计启动子高甲基化和整体低甲基化。通过微卫星分析计算等位基因丢失分数（FAL）以代表染色体不稳定性。使用相应的层次聚类分析确定分子亚类。接下来，对 25 名接受肝移植的 HCC 患者进行了分子特征与转移复发之间的关联分析；使用癌症基因组图谱 (TCGA) 中 376 例 HCC 病例的公开数据集验证了生存分析。以 TP53 突变、高 FAL 和整体低甲基化为特征的 HCC 亚型与侵袭性肿瘤特征（如血管侵犯）相关； CTNNB1 突变是进展性较慢表型的一个特征。许多分子危险因素，包括 TP53 突变、高 FAL、显着的整体低甲基化和 CTNNB1 突变的缺失，被认为可以预测接受肝移植的患者的较短无复发生存期（通过对数秩检验，p = 0.0090）。这些发现在 TCGA 的一组切除的 HCC 病例中得到了验证 (p = 0.0076)。我们的结论是，由常见遗传和表观遗传改变决定的分子风险可以预测治愈性治疗后的转移复发，并且可以作为考虑对 HCC 患者进行全身治疗的标志。
Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related deaths; an HCC subset shows rapid progression that affects survival. We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for TP53, CTNNB1, and TERT promoter mutation, methylation of 8 tumor suppressor genes, and 3 repetitive DNA sequences to estimate promoter hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was calculated to represent chromosomal instability through microsatellite analysis. Molecular subclasses were determined using corresponding and hierarchical clustering analyses. Next, twenty-five HCC patients who underwent liver transplantation were analyzed for associations between molecular characteristics and metastatic recurrence; survival analyses were validated using a publicly available dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). An HCC subtype characterized by TP53 mutation, high FAL, and global hypomethylation was associated with aggressive tumor characteristics, like vascular invasion; CTNNB1 mutation was a feature of the less-progressive phenotype. A number of molecular risk factors, including TP53 mutation, high FAL, significant global hypomethylation, and absence of CTNNB1 mutation, were noted to predict shorter recurrence-free survival in patients who underwent liver transplantation (p = 0.0090 by log-rank test). These findings were validated in a cohort of resected HCC cases from TCGA (p = 0.0076). We concluded that molecular risks determined by common genetic and epigenetic alterations could predict metastatic recurrence after curative treatments, and could be a marker for considering systemic therapy for HCC patients.
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影响因子：
--
作者：
Gentilini D;Scala S;Gaudenzi G;Garagnani P;Capri M;Cescon M;Grazi GL;Bacalini MG;Pisoni S;Dicitore A;Circelli L;Santagata S;Izzo F;Di Blasio AM;Persani L;Franceschi C;Vitale G
通讯作者：
Vitale G
影响因子：
4.6
作者：
Fernandez-Sevilla, Elena;Allard, Marc-Antoine;Adam, Rene
通讯作者：
Adam, Rene
影响因子：
4.2
作者：
Hoshida Y;Toffanin S;Lachenmayer A;Villanueva A;Minguez B;Llovet JM
通讯作者：
Llovet JM
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：
13.5
作者：
Nishida, Naoshi;Nagasaka, Takeshi;Goell, Ajay
通讯作者：
Goell, Ajay