Dataset Information

Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq.

ABSTRACT: Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313 down-regulated genes. Less DEGs were found for MD and especially for WD HCC. Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and liver cancer cells, and in biological process and pathway including metabolism, cell cycle, translation and blood coagulation. Potential drugs and genetic perturbations were found to reverse the cancer condition. The RT-PCR results showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC. This study detected and validated DEGs of PD HCC, which provides useful information on molecular mechanism of PD HCC for development of new biomarkers, therapeutic targets and drugs.

SUBMITTER: Huang Y

PROVIDER: S-EPMC5482631 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq.

Huang Yi Y Pan Jianbo J Chen Dunyan D Zheng Jiaying J Qiu Funan F Li Feng F Wu Yanan Y Wu Wenbing W Huang Xiaoli X Qian Jiang J

Oncotarget 20170501 22

Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD H ...[more]

PMID: 28415592

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Project description:Background: Methylation plays a significant role in the etiology and pathogenesis of hepatocellular carcinoma (HCC). The aim of the present study is to identify aberrantly methylated-diferentially expressed genes (DEGs) and dysregulated pathways associated with the development of HCC through integrated analysis of gene expression and methylation microarray. Method: Aberrantly methylated-DEGs were identified from gene expression microarrays (GSE62232, GSE74656) and gene methylation microarrays (GSE44909, GSE57958). Functional enrichment and pathway enrichment analyses were performed through the database of DAVID. Protein-protein interaction (PPI) network was established by STRING and visualized in Cytoscape. Subsequently, overall survival (OS) analysis of hub genes was performed by OncoLnc. Finally, we validated the expression level of CDCA5 by quantitative real-time PCR (qRT-PCR) and western blotting, and performed Immunohistochemical experiments utilizing a tissue microarray. Cell growth assay and flow cytometry were behaved to explore the function of CDCA5. Results: Aberrantly methylated-DEGs were enriched in biological process, molecular function, cellular component and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among them, cell cycle was enriched most frequently, and some terms associated with cancer were enriched, such as p53 signaling pathway, pathways in cancers, PI3K-Akt signaling pathway and AMPK signaling pathway. After survival analysis and validation in TCGA database including methylation and gene expression status, 12 hub genes were identified. Furthermore, the expression level of new gene CDCA5 was validated in HCC cell lines and hepatic normal cell lines through qRT-PCR and western blotting. In additional, immunohistochemistry experiments revealed higher CDCA5 protein expression from HCC tumor tissues compared with paracancer tissues by tissue microarray. Finally, through loss of function, we demonstrated that CDCA5 promoted proliferation by regulating the cell cycle. Conclusions: In summary, the present study implied possible aberrantly methylated-differentially expressed genes and dysregulated pathways in HCC by bioinformatics analysis and experiments, which could be helpful in understanding the molecular mechanisms underlying the development and progression of HCC. Hub genes including CDC20, AURKB, BIRC5, RRM2, MCM2, PTTG1, CDKN2A, NEK2, CENPF, RACGAP1, GNA14 and especially the new gene CDCA5 may serve as biomarkers for diagnosis, treatment and prognosis of HCC.

Dataset Information

Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq.

Publications

Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq.

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