Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome.
Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome.
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肉瘤样肝细胞癌：从临床特征到癌症基因组
DOI：
10.1002/cam4.4162
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发表时间：
2021-09
期刊：
影响因子：
4
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Zhang C;Feng S;Tu Z;Sun J;Rui T;Zhang X;Huang H;Ling Q;Zheng S
肉瘤样肝细胞癌（HCC）是一种罕见的高致死性HCC组织学亚型，其遗传病因和治疗靶点完全未知。我们纳入了我院2008年至2018年6731例病理确诊的肝癌患者中，16例接受根治性切除的肉瘤样肝癌患者。我们比较了15例肉瘤样HCC和75例倾向评分匹配的非肉瘤样HCC患者的临床特征、预后和癌症基因组。另一例并发病例采用系统发育树分析，以评估肿瘤异质性和演变。肉瘤样肝癌组肿瘤体积较大，分化程度较高，无瘤生存率（p = 0.038）和总生存率（p = 0.001）较低，肉瘤样肝癌是患者死亡的独立危险因素。将肉瘤样亚型纳入AJCC分期可提高预测患者生存率的诊断曲线。癌基因组谱显示肉瘤样HCC组中CDKN 2A、EPHA 5、FANCM和MAP 3 K1的突变率显著较高。CDKN 2A突变显著降低了肉瘤样HCC患者的无瘤生存期和总生存期。此外，46.6%的肉瘤样HCC患者在细胞周期途径基因中存在药物突变，这是Abemaciclib等人的目标。我们还发现肉瘤样和非肉瘤样病变可能起源于共同的祖先，但进展不同。我们的癌症基因组分析显示了肉瘤样HCC的特定基因组谱，其特征在于细胞周期基因特别是CDKN 2A的高突变率。结果表明，CDK 4/6抑制剂包括abemaciclib，ribociclib和palbociclib作为潜在的治疗靶点，可能有助于治疗决策。总之，肉瘤样HCC尚无特异有效的治疗方法。我们的癌症基因组分析显示了肉瘤样HCC的特定基因组谱，其特征在于细胞周期基因特别是CDKN 2A的高突变率。结果表明，CDK 4/6抑制剂包括abemaciclib，ribociclib和palbociclib作为潜在的治疗靶点，可能有助于治疗决策。
Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological confirmed HCC in year 2008 to 2018 in our hospital. We compared the clinical features, prognosis and cancer genome between 15 sarcomatoid HCC and propensity score‐matched 75 non‐sarcomatoid HCC patients. The other concurrent case was analyzed using phylogenetic tree to assess the tumor heterogeneity and evolution. Sarcomatoid HCC group showed larger tumor size, more advanced differentiation grade, lower tumor free survival (p = 0.038) and overall survival (p = 0.001), and sarcomatoid type was an independent risk factor for patient death. Integrating sarcomatoid subtype into AJCC staging could increase the diagnostic curve in predicting patient survival. The cancer genome spectrum showed sarcomatoid HCC group had significant higher mutation rates in CDKN2A, EPHA5, FANCM and MAP3K1. Mutations in CDKN2A significantly reduced tumor‐free and overall survival in sarcomatoid HCC patients. Moreover, 46.6% sarcomatoid HCC patients had druggable mutations in cell cycle pathway genes, which were targeted by Abemaciclib, et al. We also found sarcomatoid and non‐sarcomatoid lesions might originate from a common progenitor but progress differently. Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making. In summary, there is no specific and effective therapies for sarcomatoid HCC. Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
5
作者：
Li, Qi;Li, Bai;Li, Qi
通讯作者：
Li, Qi
影响因子：
13.5
作者：
Liao, Sih-Han;Su, Tung-Hung;Kao, Jia-Horng
通讯作者：
Kao, Jia-Horng
影响因子：
25.7
作者：
Marijon, Helene;Dokmak, Safi;Faivre, Sandrine
通讯作者：
Faivre, Sandrine
影响因子：
44.1
作者：
Xue Z;Vis DJ;Bruna A;Sustic T;van Wageningen S;Batra AS;Rueda OM;Bosdriesz E;Caldas C;Wessels LFA;Bernards R
通讯作者：
Bernards R