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      Identification of key genes and related pathways in hepatocarcinoma using bioinformatics analysis

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          Abstract

          Highlights:The present study described the differently expressed genes between normal tissues and hepatocellular carcinoma tissues from the level of gene transcription. The possible signaling pathways involved in the development of hepatocellular carcinoma and related molecules involved were analyzed.

          Editor’s Summary:Bioinformatics analysis is an important tool for the analysis of tumor gene expression changes in the level of signaling pathways, which help provide direction for laboratory and clinical research.

          Objective: Various treatments have greatly reduced the mortality of hepatocellular carcinoma (HCC). However, few therapies could be performed in advanced HCC. Therefore, understanding the characteristics of HCC at the level of the whole transcriptome can help prevent the progression of HCC. Methods: The aim of this study was to identify differently expressed genes and potent pathways between normal liver and HCC tissues. The gene expression profiles of GSE104627 were downloaded from Gene Expression Omnibus database. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed and protein-protein interaction network of the differentially expressed genes were constructed by Cytoscape software. Results: In total, 880 differently expressed genes were identified between normal and tumor tissues, including 554 up-regulated genes and 326 down-regulated genes. Gene Ontology analysis results showed that the up-regulated genes were significantly enriched in establishment of RNA localization, nucleic acid transport, RNA transport, RNA localization and nucleobase, nucleoside, nucleotide and nucleic acid transport. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed the up-regulated genes were enriched in axon guidance, dorso-ventral axis formation and pathways in cancer. The top 10 hub genes were identified from the protein - protein interaction network, and sub-networks revealed these genes were involved in significant pathways, including G protein-coupled receptors signaling pathway, signaling pathway via MAPK and extracellular matrix organization. Conclusion: The present study described the differently expressed genes between normal tissues and HCC tissues from the level of gene transcription. The possible signaling pathways involved in the development of HCC and related molecules involved were analyzed. However, further laboratory and clinical validation is still needed.

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          Most cited references 21

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          KEGG: kyoto encyclopedia of genes and genomes.

           M Kanehisa (2000)
          KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).
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            Cancer statistics, 2018

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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              Hepatocellular carcinoma: A global view.

              Hepatocellular carcinoma (HCC) is a global health problem, although developing countries are disproportionally affected: over 80% of HCCs occur in such regions. About three-quarters of HCCs are attributed to chronic HBV and HCV infections. In areas endemic for HCV and HBV, viral transmission occurs at an early age, and infected individuals develop HCC in mid-adulthood. As these are their most productive years of life, HCC accounts for a substantial burden on the health-care system and drain of productive capacity in the low-income and middle-income countries most affected by HCV and HBV infections. Environments with disparate resource levels require different strategies for the optimal management of HCC. In high-resource environments, guidelines from the American Association for the Study of Liver Diseases or European Association for the Study of the Liver should be applied. In intermediate-resource or low-resource environments, the fundamental focus should be on primary prevention of HCC, through universal HBV vaccination, taking appropriate precautions and antiviral treatments. In intermediate-resource and low-resource environments, the infrastructure and capacity for abdominal ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection should be established. Programs to provide targeted therapy at low cost, similar to the approach used for HIV therapy in the developing world, should be pursued.
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                Author and article information

                Contributors
                Journal
                TMR Editorial Board
                Traditional Medicine Research (Cancer)
                TMR Editorial Board (Jintang road, 99, Hedong district Tianjin,China, 300170 )
                2538-015X
                10 June 2018
                10 June 2018
                : 1
                : 2
                : 51-57
                Affiliations
                1Surgery Department of Tianjin Medical University General Hospital, Tianjin, China.
                2 Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin, China.
                Author notes
                *Correspondence to: Dan Chen, Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China. E-mail: ilvcd@ 123456163.com.

                Submitted: 20 April 2018, Accepted: 05 May 2018, Online: 10 May 2018.

                Abbreviations: HCC, Hepatocellular carcinoma; GO, Gene Ontology; DEGs, Differentially expressed genes; GEO, Gene Expression Omnibus; KEGG, Kyoto Encyclopedia of Genes and Genomes pathway; STRING, Search Tool for the Retrieval of Interacting Genes; PPI, Protein-protein interaction.

                Competing interests: Authors declare that they have no competing interests.

                Copyright: ©2018 TMR Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution Non Commercial License.

                Executive Editor: Yu-Chan Cao.

                2538-015X-1-2-51
                10.12032/TMRC201800029

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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