Identification of prognostic biomarkers in hepatitis B virus-related hepatocellular carcinoma and stratification by integrative multi-omics analysis

Miao, Ruoyu; Luo, Haitao; Zhou, Huandi; Li, Guangbing; Bu, Dechao; Yang, Xiaobo; Zhao, Xingdong; Zhang, Haohai; Liu, Song; Zhang, Ying; Zou, Zhen; Zhao, Yan; Yu, Kuntao; He, Lian; Sang, Xinting; Zhong, Shouxian; Huang, Jiefu; Wu, Yan; Miksad, Rebecca A.; Robson, Simon C.; Jiang, Chengyu; Zhao, Yi; Zhao, Haitao

doi:10.1016/j.jhep.2014.05.025

Cited by 118 publications

(119 citation statements)

References 33 publications

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“…The HBV DNA integration pattern, genomic mutations such as indels and substitutions, copy number variations, and chromosomal structure were similar in different tumors from one patient who was believed to have intrahepatic metastasis and died of recurrent disease shortly after curative resection. By contrast, the multiple tumors of the other patient had distinct HBV DNA integrations and genomic alterations, and the patient showed no recurrence for more than 2 years after the resection of multifocal HCC [26]. This study proved that comprehensive multiomics analyses can be used to characterize multifocal tumors, facilitate clinical decision making, and help implement personalized medicine.…”

Section: Intertumor Heterogeneitymentioning

confidence: 72%

Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges

Lu¹,

Hsu²,

Hsu³

et al. 2016

Liver Cancer

112

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Tumor heterogeneity in hepatocellular carcinoma (HCC), such as that found in second primary tumors after curative treatment, synchronous multifocal tumors of different clonality, or intratumor heterogeneity, poses severe challenges for the development and administration of systemic molecular targeted therapies. Various methodologies, including historical DNA ploidy analysis, integrated hepatitis B virus DNA analysis, DNA fingerprinting, and next-generation sequencing technologies, are used to explore tumor heterogeneity in HCC. It is estimated that 30%-60% of recurrent or metastatic tumors harbor clones different from the primary tumor, 22%-79% of synchronous tumors vary clonally, and 12%-66% of single tumors contain intratumor heterogeneity. Substantial intertumor and intratumor heterogeneity renders biomarker identification, which is critical for the development and administration of molecular targeted therapy, challenging when applied to a single tumor biopsy specimen. The use of circulating tumor cells or circulating tumor DNA to evaluate overall tumor heterogeneity may help resolve this problem. This article reviews previous studies of tumor heterogeneity and discusses the implications and future opportunities regarding tumor heterogeneity in HCC.

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Section: Intertumor Heterogeneitymentioning

confidence: 72%

Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges

Lu¹,

Hsu²,

Hsu³

et al. 2016

Liver Cancer

112

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show abstract

“…On the contrary, a multinodular HCC derived from IM origin is more appropriate for intervention therapy or sorafenibtargeted drug therapy [45]. Recently, Miao et al performed a whole-genome and transcriptome sequencing on 2 patients with HBV-related multifocal HCC to differentiate MO vs. IM origin [46]. Such multi-omics strategy may provide a powerful tool for the distinction of tumor clonality, but the drawbacks of the complexity of the analysis and high costs must be overcome before conventional application.…”

Section: Determination Of the Clonality Of Rhcc And Multinodular Hccmentioning

confidence: 99%

New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges

Wang

2015

Cancer Letters

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“…2 A number of genetic alterations associated with the carcinogenesis, development, and progression of HCC have been described. 3,4 In addition to genetic abnormalities, epigenetic alterations have been demonstrated to play a crucial role in the initiation, progression, and invasion of HCC. 5 As an important and common epigenetic mechanism, DNA methylation leads to the silencing of a broad range of tumor suppressor genes, which closely associate with HCC.…”

Section: Introductionmentioning

confidence: 99%