EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma
EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investiga...
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| Veröffentlicht in: | PloS one 2015-02, Vol.10 (2), p.e0117493 |
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| creator | Cha, Yin-Lian Li, Pin-Dong Yuan, Lin-Jing Zhang, Mei-Yin Zhang, Yao-Jun Rao, Hui-Lan Zhang, Hui-Zhong Zheng, X F Steven Wang, Hui-Yun |
| description | EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154-4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067-3.386; P = 0.029) in HCC patients.
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients. |
| doi_str_mv | 10.1371/journal.pone.0117493 |
| format | Article |
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Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154-4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067-3.386; P = 0.029) in HCC patients.
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0117493</identifier><identifier>PMID: 25658620</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Adolescent ; Adult ; Aged ; alpha-Fetoproteins - analysis ; Analysis ; Blotting, Western ; Breast cancer ; Cancer therapies ; Carcinogenesis ; Carcinogens ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - physiopathology ; Care and treatment ; Cell cycle ; Cell growth ; Chemotherapy ; Collaboration ; Disease Progression ; Disease-Free Survival ; Embolism ; Female ; Gene expression ; Hepatocellular carcinoma ; Humans ; Hypoxia ; Immunohistochemistry ; Laboratories ; Liver ; Liver - metabolism ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - mortality ; Liver Neoplasms - physiopathology ; Male ; Medical prognosis ; Medicine ; Middle Aged ; Mortality ; mRNA ; Neoplasm Staging ; Oncology ; Ovarian cancer ; Paraffin ; Pathology ; Patient outcomes ; Patients ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; Phosphorylation ; Proteins ; Radiation therapy ; Real-Time Polymerase Chain Reaction ; Regression analysis ; RNA ; RNA, Messenger - metabolism ; Signal transduction ; Survival ; Tissues ; TOR protein ; Tumors ; Up-Regulation ; Young Adult</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0117493</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Cha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Cha et al 2015 Cha et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-aa062c348befcf77ec9d897c1441f28c8296a2d74654a770f25019ed3c7ae633</citedby><cites>FETCH-LOGICAL-c692t-aa062c348befcf77ec9d897c1441f28c8296a2d74654a770f25019ed3c7ae633</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/PMC4319970/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319970/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25658620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cha, Yin-Lian</creatorcontrib><creatorcontrib>Li, Pin-Dong</creatorcontrib><creatorcontrib>Yuan, Lin-Jing</creatorcontrib><creatorcontrib>Zhang, Mei-Yin</creatorcontrib><creatorcontrib>Zhang, Yao-Jun</creatorcontrib><creatorcontrib>Rao, Hui-Lan</creatorcontrib><creatorcontrib>Zhang, Hui-Zhong</creatorcontrib><creatorcontrib>Zheng, X F Steven</creatorcontrib><creatorcontrib>Wang, Hui-Yun</creatorcontrib><title>EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154-4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067-3.386; P = 0.029) in HCC patients.
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>alpha-Fetoproteins - analysis</subject><subject>Analysis</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - physiopathology</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Chemotherapy</subject><subject>Collaboration</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Embolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - physiopathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>mRNA</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Paraffin</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Regression analysis</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Survival</subject><subject>Tissues</subject><subject>TOR protein</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLguDDjEmTJs2LsC6zOrCwoouv4U5628nQabpJO65-erNOd5iCguSh-fM7p5fDSZKXlMwpk_T9xg2-hWbeuRbnhFLJFXuUnFLFspnICHt8tD9JnoWwISRnhRBPk5MsF3kRH06TX4vlJV98_EJTt0OPd53HEKxrUxtSCMEZCz2W6Q_br9POOZ-Gwe_sDpoU2jItbUAImHbe1Qdhm3bQW2z7sJetMZ6dwaYZGvCpAW9s67bwPHlSQRPwxfg9S24uFzcXn2dX15-WF-dXMyNU1s8AiMgM48UKK1NJiUaVhZKGck6rrDBFpgRkpeQi5yAlqbKcUIUlMxJQMHaWvN7bdo0LekwtaCryjCqhiIjEck-UDja683YL_qd2YPWfC-drDb63pkGNJckVYawysoh5x9lWrFCEV5UQ3Kgien0Y_zastliaGIOHZmI6fWntWtdupzmjSkkSDd6MBt7dDhj6f4w8UjXEqWxbuWhmtjYYfc4zVVCZCxWp-V-ouErcWhN7U9l4PxG8mwgi0-NdX8MQgl5--_r_7PX3Kfv2iF0jNP06uGboY2HCFOR70HgXgsfqkBwl-r72D2no-9rrsfZR9uo49YPooefsN7VO_xc</recordid><startdate>20150206</startdate><enddate>20150206</enddate><creator>Cha, Yin-Lian</creator><creator>Li, Pin-Dong</creator><creator>Yuan, Lin-Jing</creator><creator>Zhang, Mei-Yin</creator><creator>Zhang, Yao-Jun</creator><creator>Rao, Hui-Lan</creator><creator>Zhang, Hui-Zhong</creator><creator>Zheng, X F Steven</creator><creator>Wang, Hui-Yun</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150206</creationdate><title>EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma</title><author>Cha, Yin-Lian ; Li, Pin-Dong ; Yuan, Lin-Jing ; Zhang, Mei-Yin ; Zhang, Yao-Jun ; Rao, Hui-Lan ; Zhang, Hui-Zhong ; Zheng, X F Steven ; Wang, Hui-Yun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-aa062c348befcf77ec9d897c1441f28c8296a2d74654a770f25019ed3c7ae633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptor Proteins, Signal Transducing - 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metabolism</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - physiopathology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>mRNA</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Paraffin</topic><topic>Pathology</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Phosphoproteins - genetics</topic><topic>Phosphoproteins - metabolism</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Regression analysis</topic><topic>RNA</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Survival</topic><topic>Tissues</topic><topic>TOR protein</topic><topic>Tumors</topic><topic>Up-Regulation</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cha, Yin-Lian</creatorcontrib><creatorcontrib>Li, Pin-Dong</creatorcontrib><creatorcontrib>Yuan, Lin-Jing</creatorcontrib><creatorcontrib>Zhang, Mei-Yin</creatorcontrib><creatorcontrib>Zhang, Yao-Jun</creatorcontrib><creatorcontrib>Rao, Hui-Lan</creatorcontrib><creatorcontrib>Zhang, Hui-Zhong</creatorcontrib><creatorcontrib>Zheng, X F Steven</creatorcontrib><creatorcontrib>Wang, Hui-Yun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cha, Yin-Lian</au><au>Li, Pin-Dong</au><au>Yuan, Lin-Jing</au><au>Zhang, Mei-Yin</au><au>Zhang, Yao-Jun</au><au>Rao, Hui-Lan</au><au>Zhang, Hui-Zhong</au><au>Zheng, X F Steven</au><au>Wang, Hui-Yun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-06</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117493</spage><pages>e0117493-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154-4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067-3.386; P = 0.029) in HCC patients.
Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25658620</pmid><doi>10.1371/journal.pone.0117493</doi><tpages>e0117493</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-02, Vol.10 (2), p.e0117493 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1652196906 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Adolescent Adult Aged alpha-Fetoproteins - analysis Analysis Blotting, Western Breast cancer Cancer therapies Carcinogenesis Carcinogens Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - physiopathology Care and treatment Cell cycle Cell growth Chemotherapy Collaboration Disease Progression Disease-Free Survival Embolism Female Gene expression Hepatocellular carcinoma Humans Hypoxia Immunohistochemistry Laboratories Liver Liver - metabolism Liver cancer Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - mortality Liver Neoplasms - physiopathology Male Medical prognosis Medicine Middle Aged Mortality mRNA Neoplasm Staging Oncology Ovarian cancer Paraffin Pathology Patient outcomes Patients Phosphoproteins - genetics Phosphoproteins - metabolism Phosphorylation Proteins Radiation therapy Real-Time Polymerase Chain Reaction Regression analysis RNA RNA, Messenger - metabolism Signal transduction Survival Tissues TOR protein Tumors Up-Regulation Young Adult |
| title | EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma |
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