Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-11, Vol.12 (23), p.23849-23871 |
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| creator | Yang, Liguang Zhang, Zhengtao Sun, Yidi Pang, Shichao Yao, Qianlan Lin, Ping Cheng, Jinming Li, Jia Ding, Guohui Hui, Lijian Li, Yixue Li, Hong |
| description | Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC. |
| doi_str_mv | 10.18632/aging.104047 |
| format | Article |
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Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.104047</identifier><identifier>PMID: 33221766</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>14-3-3 Proteins - genetics ; Biomarkers, Tumor - genetics ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - therapy ; Cell Line, Tumor ; Cell Proliferation ; Computational Biology ; Databases, Genetic ; DNA Copy Number Variations ; DNA Methylation ; E2F Transcription Factors - genetics ; Epigenesis, Genetic ; Exoribonucleases - genetics ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Genomics ; Humans ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Liver Neoplasms - therapy ; Mutation ; Neoplasm Grading ; Osteopontin - genetics ; Phenotype ; Research Paper ; Systems Integration ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Aging (Albany, NY.), 2020-11, Vol.12 (23), p.23849-23871</ispartof><rights>Copyright: © 2020 Yang et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-da9443e8617e764ae8509d0613572b7f5370ebdbd71c971807da0e0c2288f003</citedby><cites>FETCH-LOGICAL-c387t-da9443e8617e764ae8509d0613572b7f5370ebdbd71c971807da0e0c2288f003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762459/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762459/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33221766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Liguang</creatorcontrib><creatorcontrib>Zhang, Zhengtao</creatorcontrib><creatorcontrib>Sun, Yidi</creatorcontrib><creatorcontrib>Pang, Shichao</creatorcontrib><creatorcontrib>Yao, Qianlan</creatorcontrib><creatorcontrib>Lin, Ping</creatorcontrib><creatorcontrib>Cheng, Jinming</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Ding, Guohui</creatorcontrib><creatorcontrib>Hui, Lijian</creatorcontrib><creatorcontrib>Li, Yixue</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><title>Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.</description><subject>14-3-3 Proteins - genetics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Computational Biology</subject><subject>Databases, Genetic</subject><subject>DNA Copy Number Variations</subject><subject>DNA Methylation</subject><subject>E2F Transcription Factors - genetics</subject><subject>Epigenesis, Genetic</subject><subject>Exoribonucleases - genetics</subject><subject>Gene Dosage</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Regulatory Networks</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomics</subject><subject>Humans</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - therapy</subject><subject>Mutation</subject><subject>Neoplasm Grading</subject><subject>Osteopontin - genetics</subject><subject>Phenotype</subject><subject>Research Paper</subject><subject>Systems Integration</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1LxDAQhoMofqwevUqPXromTZq0F0HELxC87D1Mk2mtpMmatAv-e-uuip4y8D68k-Eh5JzRJaskL66g6323ZFRQofbIMatFmYuyqvf_zEfkJKU3SmVZCnlIjjgvCqakPCb2yY_YRRj7DWbgwX2kPmURNwguZT5s0GU2zmHMOvSYZsZmQ3BoJgcxS1NjHKQ0B6HNXnENYzDo3DY0EE3vwwCn5KCd6_Ds-12Q1f3d6vYxf355eLq9ec4Nr9SYW6iF4FhJplBJAViVtLZUMl6qolFtyRXFxjZWMVMrVlFlgSI1RVFVLaV8Qa53teupGdAa9GMEp9exHyB-6AC9_p_4_lV3YaOVkoUo67ng8rsghvcJ06iHPn2dAx7DlHQhJJeUKSpnNN-hJoaUIra_axjVWzF6K0bvxMz8xd-__dI_Jvgn8MaM8g</recordid><startdate>20201120</startdate><enddate>20201120</enddate><creator>Yang, Liguang</creator><creator>Zhang, Zhengtao</creator><creator>Sun, Yidi</creator><creator>Pang, Shichao</creator><creator>Yao, Qianlan</creator><creator>Lin, Ping</creator><creator>Cheng, Jinming</creator><creator>Li, Jia</creator><creator>Ding, Guohui</creator><creator>Hui, Lijian</creator><creator>Li, Yixue</creator><creator>Li, Hong</creator><general>Impact Journals</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201120</creationdate><title>Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma</title><author>Yang, Liguang ; Zhang, Zhengtao ; Sun, Yidi ; Pang, Shichao ; Yao, Qianlan ; Lin, Ping ; Cheng, Jinming ; Li, Jia ; Ding, Guohui ; Hui, Lijian ; Li, Yixue ; Li, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-da9443e8617e764ae8509d0613572b7f5370ebdbd71c971807da0e0c2288f003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>14-3-3 Proteins - genetics</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Computational Biology</topic><topic>Databases, Genetic</topic><topic>DNA Copy Number Variations</topic><topic>DNA Methylation</topic><topic>E2F Transcription Factors - genetics</topic><topic>Epigenesis, Genetic</topic><topic>Exoribonucleases - genetics</topic><topic>Gene Dosage</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Regulatory Networks</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomics</topic><topic>Humans</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - therapy</topic><topic>Mutation</topic><topic>Neoplasm Grading</topic><topic>Osteopontin - genetics</topic><topic>Phenotype</topic><topic>Research Paper</topic><topic>Systems Integration</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Yang, Liguang</creatorcontrib><creatorcontrib>Zhang, Zhengtao</creatorcontrib><creatorcontrib>Sun, Yidi</creatorcontrib><creatorcontrib>Pang, Shichao</creatorcontrib><creatorcontrib>Yao, Qianlan</creatorcontrib><creatorcontrib>Lin, Ping</creatorcontrib><creatorcontrib>Cheng, Jinming</creatorcontrib><creatorcontrib>Li, Jia</creatorcontrib><creatorcontrib>Ding, Guohui</creatorcontrib><creatorcontrib>Hui, Lijian</creatorcontrib><creatorcontrib>Li, Yixue</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Liguang</au><au>Zhang, Zhengtao</au><au>Sun, Yidi</au><au>Pang, Shichao</au><au>Yao, Qianlan</au><au>Lin, Ping</au><au>Cheng, Jinming</au><au>Li, Jia</au><au>Ding, Guohui</au><au>Hui, Lijian</au><au>Li, Yixue</au><au>Li, Hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-11-20</date><risdate>2020</risdate><volume>12</volume><issue>23</issue><spage>23849</spage><epage>23871</epage><pages>23849-23871</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>33221766</pmid><doi>10.18632/aging.104047</doi><tpages>23</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 14-3-3 Proteins - genetics Biomarkers, Tumor - genetics Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - therapy Cell Line, Tumor Cell Proliferation Computational Biology Databases, Genetic DNA Copy Number Variations DNA Methylation E2F Transcription Factors - genetics Epigenesis, Genetic Exoribonucleases - genetics Gene Dosage Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetic Predisposition to Disease Genomics Humans Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - therapy Mutation Neoplasm Grading Osteopontin - genetics Phenotype Research Paper Systems Integration Tumor Suppressor Protein p53 - genetics |
| title | Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma |
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