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Identification of differentially expressed genes and biological pathways in para-carcinoma tissues of HCC with different metastatic potentials.

ABSTRACT: Hepatocellular carcinoma (HCC) is a malignant tumor with extensive metastasis. Changes in the tumor microenvironment provide favorable conditions for tumor metastasis. However, the role of changes to the tumor microenvironment in HCC metastasis is yet to be elucidated. The Gene Expression Omnibus expression profile GSE5093 consists of 20 noncancerous tissues surrounding HCC tissues, including 9 metastasis-inclined microenvironment samples with detectable metastases and 11 metastasis-averse microenvironment samples without detectable metastases. The present study assessed 35 HCC samples to verify the results of chip analysis. In total, 712 upregulated and 459 downregulated genes were identified, with 1,033 nodes, 7,589 edges and 10 hub genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed genes were significantly enriched in 'cell-cell adhesion', 'cell proliferation' and 'protein binding'. The top 10 hub genes were identified via a protein-protein interaction analysis. The 3 most significant modules were identified from the protein-protein network. Moreover, an association between hub genes and patient prognosis was identified. In conclusion, these candidate genes and pathways may help elucidate the mechanisms underlying HCC metastasis and identify more options for targeted therapy.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7202278 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Identification of differentially expressed genes and biological pathways in para-carcinoma tissues of HCC with different metastatic potentials.

Liu Yan Y Deng Mingming M Wang Yimeng Y Wang Huiqin H Li Changping C Wu Hao H

Oncology letters 20200329 6

Hepatocellular carcinoma (HCC) is a malignant tumor with extensive metastasis. Changes in the tumor microenvironment provide favorable conditions for tumor metastasis. However, the role of changes to the tumor microenvironment in HCC metastasis is yet to be elucidated. The Gene Expression Omnibus expression profile GSE5093 consists of 20 noncancerous tissues surrounding HCC tissues, including 9 metastasis-inclined microenvironment samples with detectable metastases and 11 metastasis-averse micro ...[more]

PMID: 32382332

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Project description:BackgroundIntramuscular fat (IMF) is one of the important factors influencing meat quality, however, for chickens, the molecular regulatory mechanisms underlying this trait have not yet been clear. In this study, a systematic identification of differentially expressed genes (DEGs) and molecular regulatory mechanism related to IMF metabolism between Beijing-you chicken breast and thigh at 42 and 90 days of age was performed.ResultsIMF contents, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, The results showed that both IMF contents in breast at 42 and 90 d were significantly lower (P < 0.05 or P < 0.01) than those in thigh. By microarray, 515 common known DEGs and 36 DEGs related to IMF metabolism were identified between the breast and thigh at 42 and 90 d. Compared to thigh, the expression levels of PPARG had significantly down-regulated (P < 0.01) in breast, but the expression levels of RXRA and CEBPB had significantly up-regulated (P < 0.01). However, the expression levels of LPL, FABP4, THRSP, RBP7, LDLR, FABP3, CPT2 and PPARGC1A had significantly down-regulated in breast (P < 0.01), supporting that PPARG and its down-stream genes had the important regulatory function to IMF deposition. In addition, based on of DEGs, KEGG analysis revealed that PPAR signaling pathway and cell junction-related pathways (focal adhesion and ECM-receptor interaction, which play a prominent role in maintaining the integrity of tissues), might contribute to the IMF metabolism in chicken.ConclusionsOur data had screened the potential candidate genes associated with chicken IMF metabolism, and imply that IMF metabolism in chicken is regulated and mediated not only by related functional genes and PPAR pathway, but also by others involved in cell junctions. These findings establish the groundwork and provide new clues for deciphering the molecular mechanisms underlying IMF deposition in poultry. Further studies at the translational and posttranslational level are now required to validate the genes and pathways identified here.

Project description:Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality. Chemical and virus induction are two major risk factors, however, the potential molecular mechanisms of their differences remain elusive. In this study, to identify the similarities and differences between chemical and virus induced HCC models, we compared the gene expression profiles between DEN and HBx mice models, as well as the differences among tumor, para-tumor and normal tissues.We sequenced both gene and microRNA (miRNA) expression for HCC tumor tissues, para-tumor and normal liver tissues from DEN model mice (30-week-old) and downloaded the corresponding microarray expression data of HBx model from GEO database. Then differentially expressed genes (DEGs), miRNAs and transcription factors (TFs) were detected by R packages and performed functional enrichment analysis. To explore the gene regulatory network in HCC models, miRNA and TF regulatory networks were constructed by target prediction.For model comparison, although DEGs between tumor and normal tissues in DEN and HBx models only had a small part of overlapping, they shared common pathways including lipid metabolism, oxidation-reduction process and immune process. For tissue comparisons in each model, genes in oxidation-reduction process were down-regulated in tumor tissues and genes in inflammatory response showed the highest expression level in para-tumor tissues. Genes highly expressed in both tumor and para-tumor tissues in two models mainly participated in immune and inflammatory response. Genes expressed in HBx model were also involved in cell proliferation and cell migration etc. Network analysis revealed that several miRNAs such as miR-381-3p, miR-142a-3p, miR-214-3p and TFs such as Egr1, Atf3 and Klf4 were the core regulators in HCC.Through the comparative analyses, we found that para-tumor tissue is a highly inflammatory tissue while the tumor tissue is specific with both inflammatory and cancer signaling pathways. The DEN and HBx mice models have different gene expression pattern but shared pathways. This work will help to elucidate the molecular mechanisms underlying different HCC models.

Dataset Information

Identification of differentially expressed genes and biological pathways in para-carcinoma tissues of HCC with different metastatic potentials.

Publications

Identification of differentially expressed genes and biological pathways in para-carcinoma tissues of HCC with different metastatic potentials.

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