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Liu, Zhengtao
Publications (6 of 6) Show all publications
Liao, X., Yu, T., Yang, C., Huang, K., Wang, X., Han, C., . . . Peng, T. (2019). Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma. Journal of Cancer, 10(23), 5689-5704
Open this publication in new window or tab >>Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 10, no 23, p. 5689-5704Article in journal (Refereed) Published
Abstract [en]

Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods. Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification. Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients. Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

Place, publisher, year, edition, pages
IVYSPRING INT PUBL, 2019
Keywords
hepatitis B virus, hepatocellular carcinoma, DNA topoisomerase II alpha, protein regulator of cytokinesis 1, prognosis
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-263405 (URN)10.7150/jca.31287 (DOI)000490321900010 ()2-s2.0-85074342463 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20191107

Available from: 2019-11-07 Created: 2019-11-07 Last updated: 2020-03-09Bibliographically approved
Huang, K., Liao, X., Han, C., Wang, X., Yu, T., Yang, C., . . . Peng, T. (2019). Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma. Journal of Cancer, 10(6), 1453-1465
Open this publication in new window or tab >>Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 10, no 6, p. 1453-1465Article in journal (Refereed) Published
Abstract [en]

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase (POR) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of POR were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of POR in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of POR variants and mRNA expression with overall survival (OS) and recurrence-free survival (RFS). Nomograms were used to predict the prognosis of HBV-related HCC patients. Gene set enrichment analysis (GSEA) was used to investigate the mechanism of POR in HBV-related HCC prognosis. The polymorphism POR-rs1057868 was significantly associated with HBV-related HCC OS (CT/TT vs. CC, hazard ratio [HR] = 0.69, 95% confidence interval [CI] = [0.54, 0.88], P = 0.003), but not significantly associated with RFS (CT/TT vs. CC, P = 0.378). POR mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], P= 0.036), but not significantly associated with the RFS (high vs. low, P = 0.201). Two nomograms were developed to predict the HBV-related HCC OS. Furthermore, GSEA suggests that multiple gene sets were significantly enriched in liver cancer survival and recurrence, as well as POR-related target therapy in the liver. In conclusion, our study suggests that POR-rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

Place, publisher, year, edition, pages
IVYSPRING INT PUBL, 2019
Keywords
hepatocellular carcinoma, cytochrome p450 oxidoreductase, prognosis, hepatitis B virus, hepatectomy
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-246295 (URN)10.7150/jca.28919 (DOI)000459711200013 ()2-s2.0-85067286887 (Scopus ID)
Note

QC 20190325

Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2020-03-09Bibliographically approved
Liao, X., Wang, X., Huang, K., Han, C., Deng, J., Yu, T., . . . Peng, T. (2019). Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma. Journal of Cancer, 10(14), 3267-3283
Open this publication in new window or tab >>Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma
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2019 (English)In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 10, no 14, p. 3267-3283Article in journal (Refereed) Published
Abstract [en]

Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients. Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators. Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation. Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

Place, publisher, year, edition, pages
Ivyspring International Publisher, 2019
Keywords
competing endogenous RNA, hepatocellular carcinoma, bioinformatics, prognosis, TCGA
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-254121 (URN)10.7150/jca.29986 (DOI)000470088200023 ()2-s2.0-85070557159 (Scopus ID)
Note

QC 20190624

Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-10-04Bibliographically approved
Liu, Z., Zhang, C., Lee, S., Kim, W., Klevstig, M., Harzandi, A. M., . . . Mardinoglu, A. (2019). Pyruvate kinase L/R is a regulator of lipid metabolism and mitochondrial function. Metabolic engineering
Open this publication in new window or tab >>Pyruvate kinase L/R is a regulator of lipid metabolism and mitochondrial function
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2019 (English)In: Metabolic engineering, ISSN 1096-7176, E-ISSN 1096-7184Article in journal (Refereed) Published
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-248703 (URN)10.1016/j.ymben.2019.01.001 (DOI)000457633200024 ()2-s2.0-85059704001 (Scopus ID)
Note

QC 20190425

Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2020-03-03Bibliographically approved
Lee, S., Zhang, C., Liu, Z., Klevstig, M., Mukhopadhyay, B., Bergentall, M., . . . Mardinoglu, A. (2017). Network analyses identify liver-specific targets for treating liver diseases. Molecular Systems Biology
Open this publication in new window or tab >>Network analyses identify liver-specific targets for treating liver diseases
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2017 (English)In: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292Article in journal (Refereed) Published
Abstract [en]

We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
co-expression; co-regulation; HCC; metabolism; NAFLD
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-248643 (URN)10.15252/msb.20177703 (DOI)000426043900001 ()
Note

QC 20190425

Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2020-03-04Bibliographically approved
Lee, S., Zhang, C., Arif, M., Liu, Z., Benfeitas, R., Bidkhori, G., . . . Mardinoglu, A. (2017). TCSBN: a database of tissue and cancer specific biological networks. Nucleic Acids Research, 46(D1), D595-D600
Open this publication in new window or tab >>TCSBN: a database of tissue and cancer specific biological networks
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2017 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 46, no D1, p. D595-D600Article in journal (Refereed) Published
Abstract [en]

Biological networks provide new opportunities for understanding the cellular biology in both health and disease states. We generated tissue specific integrated networks (INs) for liver, muscle and adipose tissues by integratingmetabolic, regulatory and protein-protein interaction networks. We also generated human co-expression networks (CNs) for 46 normal tissues and 17 cancers to explore the functional relationships between genes as well as their relationships with biological functions, and investigate the overlap between functional and physical interactions provided by CNs and INs, respectively. These networks can be employed in the analysis of omics data, provide detailed insight into disease mechanisms by identifying the key biological components and eventually can be used in the development of efficient treatment strategies. Moreover, comparative analysis of the networks may allow for the identification of tissue-specific targets that can be used in the development of drugs with the minimum toxic effect to other human tissues. These context-specific INs and CNs are presented in an interactive website http://inetmodels.com without any limitation.

Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-248672 (URN)10.1093/nar/gkx994 (DOI)000419550700090 ()
Note

QC 20190423

Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2020-03-04Bibliographically approved
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