{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:01:48Z","timestamp":1771038108832,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T00:00:00Z","timestamp":1537660800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 104-2221-E-007-124-MY3"],"award-info":[{"award-number":["MOST 104-2221-E-007-124-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Disease Markers"],"published-print":{"date-parts":[[2018,9,23]]},"abstract":"<jats:p>The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&amp;NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&amp;PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&amp;NASH or PBC&amp;PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&amp;NASH, PBC&amp;PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&amp;NASH, PBC&amp;PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&amp;NASH, PBC&amp;PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&amp;NASH was induced through DNA methylation of <jats:italic>HIST2H2BE<\/jats:italic>, <jats:italic>HSPB1<\/jats:italic>, <jats:italic>RPL30<\/jats:italic>, and <jats:italic>ALDOB<\/jats:italic> and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&amp;PSC was induced through DNA methylation of <jats:italic>RPL23A<\/jats:italic>, <jats:italic>HIST2H2BE<\/jats:italic>, <jats:italic>TIMP1<\/jats:italic>, <jats:italic>IGF2<\/jats:italic>, <jats:italic>RPL30<\/jats:italic>, and <jats:italic>ALDOB<\/jats:italic> and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and\/or therapeutic targets.<\/jats:p>","DOI":"10.1155\/2018\/8635329","type":"journal-article","created":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T19:31:23Z","timestamp":1537731083000},"page":"1-22","source":"Crossref","is-referenced-by-count":19,"title":["Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5883-4812","authenticated-orcid":true,"given":"Cheng-Wei","family":"Li","sequence":"first","affiliation":[{"name":"National Tsing Hua University, Kuang-Fu Road, Hsinchu 30013, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Kai","family":"Chiu","sequence":"additional","affiliation":[{"name":"National Tsing Hua University, Kuang-Fu Road, Hsinchu 30013, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-6106","authenticated-orcid":true,"given":"Bor-Sen","family":"Chen","sequence":"additional","affiliation":[{"name":"National Tsing Hua University, Kuang-Fu Road, Hsinchu 30013, 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