title: Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck region, which frequently occurs in Southeast Asia, especially in the south of China. It is known that the mammalian target of rapamycin (mTOR) pathway plays a central role in regulating cellular functions, including proliferation, growth, survival, mobility, and angiogenesis. Aberrant expression of the mTOR signaling pathway molecules has been found in many types of cancer. However, whether the alterations of p-Akt, p-p70S6K and p-4EBP1 protein expression are associated with clinicopathological features and prognostic implications in NPC have not been reported. The purposes of the present study are to investigate the association between the expression of p-Akt, p-p70S6K and p-4EBP1 proteins and clinicopathological features in NPC by immunohistochemistry. The results showed that the positive percentage of p-Akt, p-p70S6K and p-4EBP1 proteins expression in NPC (47.2%, 73.0% and 61.7%, respectively) was significantly higher than that in the non-cancerous nasopharyngeal control tissue (33.3%, 59.1% and 47.0%, respectively). There was a significantly higher positive expression of p-Akt in undifferentiated non-keratinizing nasopharyngeal carcinoma than that in differentiated non-keratinizing nasopharyngeal carcinoma (P = 0.014). Additionally, positive expression of p-p70S6K and p-4EBP1 proteins, and positive expression of either of p-Akt, p-p70S6K and p-4EBP1 were significantly correlated inversely with overall survival rates of NPC patients (P = 0.023, P = 0.033, P = 0.008, respectively). Spearman's rank correlation test showed that expression of p-Akt in NPC was significantly associated with expression of p-p70S6K (r = 0.263, P<0.001) and p-4EBP1(r = 0.284, P<0.001). Also there was an obviously positive association between expression of p-p70S6K and p-4EBP1 proteins in NPC (r = 0.286, P<0.001). Multivariate Cox regression analysis further identified positive expression of p-4EBP1 and p-p70S6K proteins were the independent poor prognostic factors for NPC (P = 0.043, P = 0.027, respectively). Taken together, high expression of p-p70S6K and p-4EBP1 proteins may act as valuable independent biomarkers to predict a poor prognosis of NPC.
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Oncology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Shuzhou
authors.initials: S
authors.lastname: Chu
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Otorhinolaryngology, Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Pathology, Basic Medical College of Central South University, Changsha, Hunan, China.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma; D018797:Cell Cycle Proteins; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1