The Endless Sources of Hepatocellular Carcinoma Heterogeneity.
The Endless Sources of Hepatocellular Carcinoma Heterogeneity.
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DOI：
10.3390/cancers13112621
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发表时间：
2021-05-26
期刊：
影响因子：
5.2
通讯作者：
Lujambio A
中科院分区：
文献类型：
--
作者：
Barcena-Varela M;Lujambio A
肝癌中的肿瘤异质性是导致该疾病患者高致死率的主要原因。治疗结果受到这种异质性的极大影响，这使得患者分层和反应预测变得复杂。更好地了解导致这种异质性的所有因素对于提高我们对肝癌的了解至关重要，从而优化患者的治疗结果。肝细胞癌（HCC）是一个全球性的健康问题。发病率不断增加，目前的治疗方案给患者带来的好处有限。肿瘤异质性在这种情况下发挥着核心作用，限制了预测生物标志物的可用性并使选择最合适治疗方案的标准复杂化。 HCC 异质性发生在不同的水平：群体内（患者间异质性）和同一患者的肿瘤内（患者内和肿瘤内异质性）。该领域的专家做出了许多努力，根据临床病理特征和分子特征对患者进行分类；然而，要整合肿瘤微环境的复杂性所产生的肿瘤外异质性，还有很多工作要做，这在疾病的发病机制和治疗反应中发挥着关键作用。在这篇综述中，我们总结了肝癌最常见病因的肿瘤内在和外在异质性来源，并总结了关于肝癌细胞进化轨迹以及微生物组和宿主免疫系统等肿瘤外在因素影响的最新发现。我们进一步强调了新型高通量方法的潜力，有助于更好地了解这种破坏性疾病并改善患者的临床管理。
Tumor heterogeneity in liver cancer is a major contributor to the high lethality rate found in patients suffering from this disease. The therapeutic outcomes are drastically affected by this heterogeneity, which complicates patient stratification and response prediction. Better understanding of all the factors that can contribute to this heterogeneity will be critical to improve our understanding of liver cancer, in order to optimize the outcome of patients. Hepatocellular carcinoma (HCC) represents a global health problem. The incidence keeps increasing and current therapeutic options confer limited benefits to the patients. Tumor heterogeneity plays a central role in this context, limiting the availability of predictive biomarkers and complicating the criteria used to choose the most suitable therapeutic option. HCC heterogeneity occurs at different levels: within the population (inter-patient heterogeneity) and within tumors from the same patient (intra-patient and intra-tumor heterogeneity). Experts in the field have made many efforts to classify the patients based on clinicopathological characteristics and molecular signatures; however, there is still much work ahead to be able to integrate the extra-tumor heterogeneity that emerges from the complexity of the tumor microenvironment, which plays a critical role in the pathogenesis of the disease and therapy responses. In this review, we summarize tumor intrinsic and extrinsic sources of heterogeneity of the most common etiologies of HCC and summarize the most recent discoveries regarding the evolutionary trajectory of liver cancer cells and the influence of tumor-extrinsic factors such as the microbiome and the host immune system. We further highlight the potential of novel high-throughput methodologies to contribute to a better understanding of this devastating disease and to the improvement of the clinical management of patients.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
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：
29.4
作者：
Ding, Xiaofan;He, Mian;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
64.8
作者：
BRESSAC, B;KEW, M;OZTURK, M
通讯作者：
OZTURK, M
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影响因子：
5.2
作者：
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通讯作者：
Avila MA