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Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma
The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor...
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Published in: | PloS one 2015-03, Vol.10 (3), p.e0119405-e0119405 |
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description | The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P |
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fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1664930451</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A423859311</galeid><doaj_id>oai_doaj_org_article_ca873d51f34c4836b934977470da5061</doaj_id><sourcerecordid>A423859311</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-a79c98ec98328bdfb01d0390eba54e1c477106d63b58f101fb5bce4daf1626c3</originalsourceid><addsrcrecordid>eNqNk2Fv1CAYxxujcXP6DYySmBh9cScUSsubJZdF3SWX7KKLbwmltOXSgw6obq_86lKvW65mLwwhEPg9f-DP8yTJawSXCOfo084Ozohu2VujlhAhRmD2JDlFDKcLmkL89Gh-krzwfgdhhgtKnycnaZYznGN6mvxelco5YQJQt71T3mtrgK3B9nKz3SIgTHWYpkBa51QngvLglw4t6K11oHe2MdZrD7QBvQhamTDtt3e97Vvh7kyjRAf8zSD2dvBAqq4DUjipjd2Ll8mzWnRevZrGs-T6y-fri8vF5urr-mK1WUjK0rAQOZOsULHjtCiruoSogphBVYqMKCRJniNIK4rLrKgRRHWZlVKRStSIplTis-TtQbbvrOeTdZ4jSgnDkGQoEusDUVmx473T-3h1boXmfxesa7hwQctOcSmKHFcZqjGRpMC0ZJiwPCc5rEQG6ah1Pp02lHtVyWiKE91MdL5jdMsb-5MTTIuckCjwYRJw9mZQPvC99qNxwqjo4XhvmrIsZSyi7_5BH3_dRDUiPkCb2sZz5SjKVyTFRcYwGqnlI1RsldprGfOs1nF9FvBxFhCZoG5DIwbv-fr7t_9nr37M2fdHbBvzJ7TedkOI2ennIDmA0lnvnaofTEaQj2Vy7wYfy4RPZRLD3hx_0EPQfV3gPztLDdQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1664930451</pqid></control><display><type>article</type><title>Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Zhou, Jieyu ; Yu, Xuemin ; Wang, Juan ; Li, Tao ; Jin, Tong ; Lei, Dapeng ; Pan, Xinliang</creator><contributor>Toland, Amanda Ewart</contributor><creatorcontrib>Zhou, Jieyu ; Yu, Xuemin ; Wang, Juan ; Li, Tao ; Jin, Tong ; Lei, Dapeng ; Pan, Xinliang ; Toland, Amanda Ewart</creatorcontrib><description>The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119405</identifier><identifier>PMID: 25793736</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Adult ; Aged ; Anticancer properties ; Apoptosis ; Biomarkers ; Breast cancer ; Cancer therapies ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - therapy ; Cell cycle ; Cell growth ; Cervix ; Correlation ; Correlation coefficient ; Correlation coefficients ; Female ; Follow-Up Studies ; Gene Expression ; Homology ; Humans ; Hypopharyngeal Neoplasms - genetics ; Hypopharyngeal Neoplasms - mortality ; Hypopharyngeal Neoplasms - pathology ; Hypopharyngeal Neoplasms - therapy ; Immunohistochemistry ; Isoforms ; Kaplan-Meier Estimate ; Kinases ; Leucine ; Lymph nodes ; Male ; Medical prognosis ; Metastases ; Metastasis ; Middle Aged ; Mucosa ; Multivariate analysis ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Otolaryngology ; Patients ; Phosphatase ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Pleckstrin ; Polymerase chain reaction ; Prognosis ; Prostate cancer ; Protein Isoforms ; Protein phosphatase ; Proteins ; Radiation therapy ; Reverse transcription ; RNA ; RNA, Messenger - genetics ; Squamous cell carcinoma ; Surgery ; Survival analysis ; Throat cancer ; Tissues ; Tumors</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0119405-e0119405</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Zhou 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 Zhou et al 2015 Zhou et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a79c98ec98328bdfb01d0390eba54e1c477106d63b58f101fb5bce4daf1626c3</citedby><cites>FETCH-LOGICAL-c692t-a79c98ec98328bdfb01d0390eba54e1c477106d63b58f101fb5bce4daf1626c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1664930451/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1664930451?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25793736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Toland, Amanda Ewart</contributor><creatorcontrib>Zhou, Jieyu</creatorcontrib><creatorcontrib>Yu, Xuemin</creatorcontrib><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>Jin, Tong</creatorcontrib><creatorcontrib>Lei, Dapeng</creatorcontrib><creatorcontrib>Pan, Xinliang</creatorcontrib><title>Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes.</description><subject>Aberration</subject><subject>Adult</subject><subject>Aged</subject><subject>Anticancer properties</subject><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cervix</subject><subject>Correlation</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Expression</subject><subject>Homology</subject><subject>Humans</subject><subject>Hypopharyngeal Neoplasms - genetics</subject><subject>Hypopharyngeal Neoplasms - mortality</subject><subject>Hypopharyngeal Neoplasms - pathology</subject><subject>Hypopharyngeal Neoplasms - therapy</subject><subject>Immunohistochemistry</subject><subject>Isoforms</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Leucine</subject><subject>Lymph nodes</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Multivariate analysis</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Staging</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Otolaryngology</subject><subject>Patients</subject><subject>Phosphatase</subject><subject>Phosphoprotein Phosphatases - genetics</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Pleckstrin</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Protein Isoforms</subject><subject>Protein phosphatase</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Reverse transcription</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>Squamous cell carcinoma</subject><subject>Surgery</subject><subject>Survival analysis</subject><subject>Throat cancer</subject><subject>Tissues</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk2Fv1CAYxxujcXP6DYySmBh9cScUSsubJZdF3SWX7KKLbwmltOXSgw6obq_86lKvW65mLwwhEPg9f-DP8yTJawSXCOfo084Ozohu2VujlhAhRmD2JDlFDKcLmkL89Gh-krzwfgdhhgtKnycnaZYznGN6mvxelco5YQJQt71T3mtrgK3B9nKz3SIgTHWYpkBa51QngvLglw4t6K11oHe2MdZrD7QBvQhamTDtt3e97Vvh7kyjRAf8zSD2dvBAqq4DUjipjd2Ll8mzWnRevZrGs-T6y-fri8vF5urr-mK1WUjK0rAQOZOsULHjtCiruoSogphBVYqMKCRJniNIK4rLrKgRRHWZlVKRStSIplTis-TtQbbvrOeTdZ4jSgnDkGQoEusDUVmx473T-3h1boXmfxesa7hwQctOcSmKHFcZqjGRpMC0ZJiwPCc5rEQG6ah1Pp02lHtVyWiKE91MdL5jdMsb-5MTTIuckCjwYRJw9mZQPvC99qNxwqjo4XhvmrIsZSyi7_5BH3_dRDUiPkCb2sZz5SjKVyTFRcYwGqnlI1RsldprGfOs1nF9FvBxFhCZoG5DIwbv-fr7t_9nr37M2fdHbBvzJ7TedkOI2ennIDmA0lnvnaofTEaQj2Vy7wYfy4RPZRLD3hx_0EPQfV3gPztLDdQ</recordid><startdate>20150320</startdate><enddate>20150320</enddate><creator>Zhou, Jieyu</creator><creator>Yu, Xuemin</creator><creator>Wang, Juan</creator><creator>Li, Tao</creator><creator>Jin, Tong</creator><creator>Lei, Dapeng</creator><creator>Pan, Xinliang</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150320</creationdate><title>Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma</title><author>Zhou, Jieyu ; Yu, Xuemin ; Wang, Juan ; Li, Tao ; Jin, Tong ; Lei, Dapeng ; Pan, Xinliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a79c98ec98328bdfb01d0390eba54e1c477106d63b58f101fb5bce4daf1626c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aberration</topic><topic>Adult</topic><topic>Aged</topic><topic>Anticancer properties</topic><topic>Apoptosis</topic><topic>Biomarkers</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cervix</topic><topic>Correlation</topic><topic>Correlation coefficient</topic><topic>Correlation coefficients</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Expression</topic><topic>Homology</topic><topic>Humans</topic><topic>Hypopharyngeal Neoplasms - genetics</topic><topic>Hypopharyngeal Neoplasms - mortality</topic><topic>Hypopharyngeal Neoplasms - pathology</topic><topic>Hypopharyngeal Neoplasms - therapy</topic><topic>Immunohistochemistry</topic><topic>Isoforms</topic><topic>Kaplan-Meier Estimate</topic><topic>Kinases</topic><topic>Leucine</topic><topic>Lymph nodes</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mucosa</topic><topic>Multivariate analysis</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Staging</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Otolaryngology</topic><topic>Patients</topic><topic>Phosphatase</topic><topic>Phosphoprotein Phosphatases - genetics</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Pleckstrin</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Protein Isoforms</topic><topic>Protein phosphatase</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Reverse transcription</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>Squamous cell carcinoma</topic><topic>Surgery</topic><topic>Survival analysis</topic><topic>Throat cancer</topic><topic>Tissues</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Jieyu</creatorcontrib><creatorcontrib>Yu, Xuemin</creatorcontrib><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>Jin, Tong</creatorcontrib><creatorcontrib>Lei, Dapeng</creatorcontrib><creatorcontrib>Pan, Xinliang</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>Science In Context</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</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 Complete (ProQuest Database)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest 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)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Agriculture & Environmental Science Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest 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</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>ProQuest Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</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>Zhou, Jieyu</au><au>Yu, Xuemin</au><au>Wang, Juan</au><au>Li, Tao</au><au>Jin, Tong</au><au>Lei, Dapeng</au><au>Pan, Xinliang</au><au>Toland, Amanda Ewart</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-20</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0119405</spage><epage>e0119405</epage><pages>e0119405-e0119405</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25793736</pmid><doi>10.1371/journal.pone.0119405</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-03, Vol.10 (3), p.e0119405-e0119405 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1664930451 |
source | Publicly Available Content (ProQuest); PubMed Central |
subjects | Aberration Adult Aged Anticancer properties Apoptosis Biomarkers Breast cancer Cancer therapies Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - therapy Cell cycle Cell growth Cervix Correlation Correlation coefficient Correlation coefficients Female Follow-Up Studies Gene Expression Homology Humans Hypopharyngeal Neoplasms - genetics Hypopharyngeal Neoplasms - mortality Hypopharyngeal Neoplasms - pathology Hypopharyngeal Neoplasms - therapy Immunohistochemistry Isoforms Kaplan-Meier Estimate Kinases Leucine Lymph nodes Male Medical prognosis Metastases Metastasis Middle Aged Mucosa Multivariate analysis Neoplasm Grading Neoplasm Metastasis Neoplasm Staging Nuclear Proteins - genetics Nuclear Proteins - metabolism Otolaryngology Patients Phosphatase Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Pleckstrin Polymerase chain reaction Prognosis Prostate cancer Protein Isoforms Protein phosphatase Proteins Radiation therapy Reverse transcription RNA RNA, Messenger - genetics Squamous cell carcinoma Surgery Survival analysis Throat cancer Tissues Tumors |
title | Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma |
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