title: Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma.
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.
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China ; Department of Biochemistry of Changzhi Medical College, Changzhi, Shanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Oncology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, the Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012008:Recurrence; D055815:Young Adult
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases