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Functional Genomic Complexity Defines Intratumor Heterogeneity and Tumor Aggressiveness in Liver Cancer.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-15 , DOI: 10.1038/s41598-019-52578-8 So Mee Kwon 1, 2 , Anuradha Budhu 1 , Hyun Goo Woo 1, 3 , Jittiporn Chaisaingmongkol 1, 4, 5 , Hien Dang 1 , Marshonna Forgues 1 , Curtis C Harris 1 , Gao Zhang 6 , Noam Auslander 7 , Eytan Ruppin 7 , Chulabhorn Mahidol 4 , Mathuros Ruchirawat 4, 5 , Xin Wei Wang 1
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-15 , DOI: 10.1038/s41598-019-52578-8 So Mee Kwon 1, 2 , Anuradha Budhu 1 , Hyun Goo Woo 1, 3 , Jittiporn Chaisaingmongkol 1, 4, 5 , Hien Dang 1 , Marshonna Forgues 1 , Curtis C Harris 1 , Gao Zhang 6 , Noam Auslander 7 , Eytan Ruppin 7 , Chulabhorn Mahidol 4 , Mathuros Ruchirawat 4, 5 , Xin Wei Wang 1
Affiliation
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Chronic inflammation and chromosome aneuploidy are major traits of primary liver cancer (PLC), which represent the second most common cause of cancer-related death worldwide. Increased cancer fitness and aggressiveness of PLC may be achieved by enhancing tumoral genomic complexity that alters tumor biology. Here, we developed a scoring method, namely functional genomic complexity (FGC), to determine the degree of molecular heterogeneity among 580 liver tumors with diverse ethnicities and etiologies by assessing integrated genomic and transcriptomic data. We found that tumors with higher FGC scores are associated with chromosome instability and TP53 mutations, and a worse prognosis, while tumors with lower FGC scores have elevated infiltrating lymphocytes and a better prognosis. These results indicate that FGC scores may serve as a surrogate to define genomic heterogeneity of PLC linked to chromosomal instability and evasion of immune surveillance. Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy.
中文翻译：
功能基因组复杂性定义了肝癌的瘤内异质性和肿瘤侵袭性。
慢性炎症和染色体非整倍性是原发性肝癌（PLC）的主要特征，是全球癌症相关死亡的第二大常见原因。提高癌症适应性和 PLC 的侵袭性可以通过增强改变肿瘤生物学的肿瘤基因组复杂性来实现。在这里，我们开发了一种评分方法，即功能基因组复杂性（FGC），通过评估整合的基因组和转录组数据来确定 580 个不同种族和病因的肝脏肿瘤之间的分子异质性程度。我们发现FGC评分较高的肿瘤与染色体不稳定和TP53突变有关，预后较差，而FGC评分较低的肿瘤浸润淋巴细胞增多，预后较好。这些结果表明，FGC 评分可以作为定义与染色体不稳定和逃避免疫监视相关的 PLC 基因组异质性的替代指标。我们的研究结果表明，仅根据大量基因组和转录组数据即可定义肝癌的基因组异质性和相应的肿瘤生物学。我们的数据还为应用这种方法来调查肝脏肿瘤免疫力和对患者进行免疫治疗分层提供了理论基础。
更新日期：2019-11-15
中文翻译：
功能基因组复杂性定义了肝癌的瘤内异质性和肿瘤侵袭性。
慢性炎症和染色体非整倍性是原发性肝癌（PLC）的主要特征，是全球癌症相关死亡的第二大常见原因。提高癌症适应性和 PLC 的侵袭性可以通过增强改变肿瘤生物学的肿瘤基因组复杂性来实现。在这里，我们开发了一种评分方法，即功能基因组复杂性（FGC），通过评估整合的基因组和转录组数据来确定 580 个不同种族和病因的肝脏肿瘤之间的分子异质性程度。我们发现FGC评分较高的肿瘤与染色体不稳定和TP53突变有关，预后较差，而FGC评分较低的肿瘤浸润淋巴细胞增多，预后较好。这些结果表明，FGC 评分可以作为定义与染色体不稳定和逃避免疫监视相关的 PLC 基因组异质性的替代指标。我们的研究结果表明，仅根据大量基因组和转录组数据即可定义肝癌的基因组异质性和相应的肿瘤生物学。我们的数据还为应用这种方法来调查肝脏肿瘤免疫力和对患者进行免疫治疗分层提供了理论基础。
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