Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellu...
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| Veröffentlicht in: | PloS one 2014-02, Vol.9 (2), p.e89220-e89220 |
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| creator | Zheng, Jun Li, Jiao Xu, Lina Xie, Guiyuan Wen, Qiuyuan Luo, Jiadi Li, Duo Huang, Donghai Fan, Songqing |
| description | Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman's rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and therapeutic targets for developing the valid treatment strategies. |
| doi_str_mv | 10.1371/journal.pone.0089220 |
| format | Article |
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The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman's rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and therapeutic targets for developing the valid treatment strategies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0089220</identifier><identifier>PMID: 24551240</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Bioindicators ; Biology ; Biomarkers ; Breast cancer ; Cancer metastasis ; Carcinoma ; Cell cycle ; Cell growth ; Cell survival ; Chemotherapy ; Correlation ; Epithelium ; Ethics ; Eukaryotic Initiation Factor-4E - metabolism ; Female ; Head ; Humans ; Immunohistochemistry ; Informed consent ; Initiation factor eIF-4E ; Intracellular Signaling Peptides and Proteins - metabolism ; Kaplan-Meier Estimate ; Kinases ; Lymph ; Lymph nodes ; Lymphatic Metastasis - pathology ; Lymphatic system ; Male ; MAP kinase ; Medical prognosis ; Medicine ; Metastases ; Metastasis ; Middle Aged ; Mnk1 protein ; Multivariate Analysis ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms - metabolism ; Nasopharyngeal Neoplasms - pathology ; Neck ; Otolaryngology ; Pathogenesis ; Pathology ; Phosphorylation ; Phosphotransferases ; Prognosis ; Proportional Hazards Models ; Prostate cancer ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Radiation therapy ; Recurrence ; Survival ; Throat cancer ; Tissues ; Transformation ; Transformations (mathematics) ; Translation (Genetics) ; Young Adult</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e89220-e89220</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Zheng 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>2014 Zheng et al 2014 Zheng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-90a3e435d4a09fd32dc0fe823c26d3a01097cacfa538165477f11b0214bbb79a3</citedby><cites>FETCH-LOGICAL-c692t-90a3e435d4a09fd32dc0fe823c26d3a01097cacfa538165477f11b0214bbb79a3</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/PMC3925237/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925237/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24551240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Jun</creatorcontrib><creatorcontrib>Li, Jiao</creatorcontrib><creatorcontrib>Xu, Lina</creatorcontrib><creatorcontrib>Xie, Guiyuan</creatorcontrib><creatorcontrib>Wen, Qiuyuan</creatorcontrib><creatorcontrib>Luo, Jiadi</creatorcontrib><creatorcontrib>Li, Duo</creatorcontrib><creatorcontrib>Huang, Donghai</creatorcontrib><creatorcontrib>Fan, Songqing</creatorcontrib><title>Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman's rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and therapeutic targets for developing the valid treatment strategies.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Breast cancer</subject><subject>Cancer metastasis</subject><subject>Carcinoma</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell survival</subject><subject>Chemotherapy</subject><subject>Correlation</subject><subject>Epithelium</subject><subject>Ethics</subject><subject>Eukaryotic Initiation Factor-4E - metabolism</subject><subject>Female</subject><subject>Head</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Informed consent</subject><subject>Initiation factor eIF-4E</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Lymph</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis - pathology</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mnk1 protein</subject><subject>Multivariate Analysis</subject><subject>Nasopharyngeal Carcinoma</subject><subject>Nasopharyngeal Neoplasms - metabolism</subject><subject>Nasopharyngeal Neoplasms - pathology</subject><subject>Neck</subject><subject>Otolaryngology</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Phosphorylation</subject><subject>Phosphotransferases</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Prostate cancer</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Recurrence</subject><subject>Survival</subject><subject>Throat cancer</subject><subject>Tissues</subject><subject>Transformation</subject><subject>Transformations (mathematics)</subject><subject>Translation (Genetics)</subject><subject>Young 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Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma</title><author>Zheng, Jun ; Li, Jiao ; Xu, Lina ; Xie, Guiyuan ; Wen, Qiuyuan ; Luo, Jiadi ; Li, Duo ; Huang, Donghai ; Fan, Songqing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-90a3e435d4a09fd32dc0fe823c26d3a01097cacfa538165477f11b0214bbb79a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Bioindicators</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Breast cancer</topic><topic>Cancer metastasis</topic><topic>Carcinoma</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell survival</topic><topic>Chemotherapy</topic><topic>Correlation</topic><topic>Epithelium</topic><topic>Ethics</topic><topic>Eukaryotic Initiation 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Jiadi</au><au>Li, Duo</au><au>Huang, Donghai</au><au>Fan, Songqing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-14</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e89220</spage><epage>e89220</epage><pages>e89220-e89220</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman's rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and therapeutic targets for developing the valid treatment strategies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24551240</pmid><doi>10.1371/journal.pone.0089220</doi><tpages>e89220</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-02, Vol.9 (2), p.e89220-e89220 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1498237355 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Adult Aged Aged, 80 and over Analysis Bioindicators Biology Biomarkers Breast cancer Cancer metastasis Carcinoma Cell cycle Cell growth Cell survival Chemotherapy Correlation Epithelium Ethics Eukaryotic Initiation Factor-4E - metabolism Female Head Humans Immunohistochemistry Informed consent Initiation factor eIF-4E Intracellular Signaling Peptides and Proteins - metabolism Kaplan-Meier Estimate Kinases Lymph Lymph nodes Lymphatic Metastasis - pathology Lymphatic system Male MAP kinase Medical prognosis Medicine Metastases Metastasis Middle Aged Mnk1 protein Multivariate Analysis Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - metabolism Nasopharyngeal Neoplasms - pathology Neck Otolaryngology Pathogenesis Pathology Phosphorylation Phosphotransferases Prognosis Proportional Hazards Models Prostate cancer Protein-Serine-Threonine Kinases - metabolism Proteins Radiation therapy Recurrence Survival Throat cancer Tissues Transformation Transformations (mathematics) Translation (Genetics) Young Adult |
| title | Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma |
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