Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma

Yang, Biwei; Li, Meiyi; Tang, Wenyi; Liu, Weixin; Zhang, Si; Chen, Luonan; Xia, Jinglin

doi:10.1038/s41467-018-03024-2

Cited by 181 publications

(170 citation statements)

References 55 publications

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“…Many studies have revealed that metastasis and recurrence are the most important reasons for the death of patients with HCC . Therefore, we examined the function of NCAPH in migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

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Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

Sun

Huang

Wang

et al. 2019

Molecular Carcinogenesis

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Non‐SMC condensing I complex subunit H (NCAPH) is a member of the Barr protein family and part of the condensin I complex. The upregulation of NCAPH is associated with poor prognosis in patients with colon cancer. However, the relationship between NCAPH and hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore NCAPH expression in HCC tissues and to investigate NCAPH functions in HCC cells. In this study, we found that high expression of NCAPH in HCC indicated worse prognosis via bioinformatics analysis. Consistently, quantitative real‐time polymerase chain reaction assays in 20 pairs of HCC specimens and the immunohistochemical analysis of 100 HCC tissues showed the upregulation of NCAPH. We established stable NCAPH‐overexpressing and NCAPH knockdown cell lines. Cell Counting Kit‐8 assays and colony formation assay were performed to analyze cell proliferation. Migration and invasion were analyzed by Transwell assays. Subcutaneous xenograft models were used to explore the role of NCAPH in tumor formation in vivo. Our results showed that NCAPH promoted tumor proliferation, migration, and invasion in vitro and in vivo. In conclusion, our findings indicate that NCAPH could serve as a novel prognostic biomarker and a potential therapeutic target for patients with HCC.

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Section: Discussionmentioning

confidence: 99%

“…Many studies have revealed that metastasis and recurrence are the most important reasons for the death of patients with HCC. 18,19 Therefore, we examined the function of NCAPH in migration and invasion. The results demonstrated that NCAPH could promote the ability of HCC cells to migrate and invade in vitro.…”

Section: Discussionmentioning

confidence: 99%

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

Sun

Huang

Wang

et al. 2019

Molecular Carcinogenesis

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“…Several previous studies have revealed that solid subtype LUAD is more likely to harbor KRAS and TP53 mutations but less likely to harbor EGFR mutations compared to the nonsolid subtypes . However, there is still a lack of effective therapeutic agents targeting KRAS because the blockage of key KRAS effectors may lead to the activation of compensatory or parallel pathways . In order to discover more druggable mutated genes, we identified 356 significantly differentially mutated genes in the TCGA cohort and 639 in the BI cohort.…”

Section: Discussionmentioning

confidence: 99%

“…9 However, there is still a lack of effective therapeutic agents targeting KRAS because the blockage of key KRAS effectors may lead to the activation of compensatory or parallel pathways. 28 In order to discover more druggable mutated genes, we identified 356 significantly differentially mutated genes in the TCGA cohort and 639 in the BI cohort. Only 38 genes overlapped in the two groups.…”

Section: Discussionmentioning

confidence: 99%

Genetic analyses of differences between solid and nonsolid predominant lung adenocarcinomas

Luo

Shi

et al. 2018

Thoracic Cancer

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BackgroundSolid predominant lung adenocarcinomas (LUAD) have distinct histopathological and clinical characteristics compared with nonsolid subtypes. A comprehensive comparison of altered genes found in solid and nonsolid subtypes has not previously been performed. In this study, we analyzed differences in gene expression, genetic mutations, and DNA methylation to better understand the risk factors for these two subtypes of LUAD.MethodsDifferentially expressed genes (DEGs) and differentially mutated genes (DMGs) were analyzed from RNA‐seq data downloaded from The Cancer Genome Atlas (TCGA) and Broad Institute database. To understand the functional significance of molecular changes, we examined the DEGs and DMGs with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis.ResultsA total of 184 patients in the TCGA cohort and 140 patients in the Broad Institute cohort were included in this study. We identified 75 DEGs, of which 15 were upregulated and 56 downregulated in the solid group relative to the nonsolid group. The DEGs were mainly involved in the regulation of water and fluid transport. We discovered 38 significantly differentially expressed genes that overlapped in the two groups. The DMGs were mainly enriched for pathways involved in cell–cell adhesion, cell adhesion, biological adhesion, and hemophilic cell adhesion. We additionally discovered nine significantly methylated genes between solid and nonsolid LUAD.ConclusionsOur study identified distinct DEGs, DMGs, and methylation genes for solid and nonsolid LUAD subtypes. These findings improve our understanding of the different carcinogenesis mechanisms in LUAD and will help to develop new therapeutic strategies.

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“…Gene regulatory network is turned by temporal transcription with noise. By modelling dynamic network properties (or correlated gene-oscillation) along with disease states (grouped phenotypes), our group and others have identified transcriptomic signals for critical state transitions (Chen, Liu et al, 2012, Mojtahedi, Skupin et al, 2016, Yang, Li et al, 2018. Some of these signals showed clinical significances, for instance epithelial-mesenchymal transition in cancer progression (Jolly, Ware et al, 2017, Tian, Zhou et al, 2018, metabolic transition between tumor and microenvironment (Kianercy, Veltri et al, 2014), and tumor-immune interaction (Lesterhuis et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Tipping-point analysis uncovers critical transition signals from gene expression profiles

Yang

Wang

Goldstein

et al. 2019

Preprint

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Highlights: We adopt 'tipping-point' theory to identify distribution-transition in disease regulatory states  Critical transcriptional transition happens between low-risk and a high-risk neuroblastoma states  A critical transition signal (CTS) based on coherent expression of genes and lncRNAs shows prognostic significance  GWAS-scans with the CTS unveiled five overlooked genes and four lncRNAs with promising clinical implications  We propose a CTS-amplifier model that unveils complex but mastering transregulation in disease AbstractTipping-point models have had success identifying transcriptional critical-transition signal (CTS) in tumor phenotypes using time-course data. Can these mathematical models be adopted to cross-sectional transcriptome profiles? Furthermore, can the 2 CTS analysis that characterizes tumor progression be applied to lncRNA-expression patterns? This study introduces a novel network-perturbation signature (NPS) scoring scheme to model a phenotype-defined tumor regulatory system. Applying NPS to neuroblastoma transcriptome of two patient populations yielded two CTSs that reproducibly identified a critical system transition between the low-risk and a high-risk state. The coherent expression pattern of one specific CTS, consisting of mRNA and lncRNA components, showed prognostic significance. Associating GWAS-scans with the CTS unveiled four overlooked intergenic loci and five genes with promising clinical significance. Additionally, a new mechanism of 'CTS-amplifier' is proposed, modeling how CTS-transcript fluctuation response to complex master regulators such as c-MYC and HNF4A uniquely in the transition state. Overall, NPS is a powerful computational approach that provides a breakthrough in phenomenological analysis of collective regulatory trajectory by applying 'tipping-point' theory to '-omics' data.

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Dynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma

Cited by 181 publications

References 55 publications

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

Genetic analyses of differences between solid and nonsolid predominant lung adenocarcinomas

Tipping-point analysis uncovers critical transition signals from gene expression profiles

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