PMID- 25165983 OWN - NLM STAT- MEDLINE DCOM- 20151117 LR - 20220408 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 8 DP - 2014 TI - Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma. PG - e106098 LID - 10.1371/journal.pone.0106098 [doi] LID - e106098 AB - 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. FAU - Wang, Weiyuan AU - Wang W AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Wen, Qiuyuan AU - Wen Q AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Xu, Lina AU - Xu L AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Xie, Guiyuan AU - Xie G AD - Department of Oncology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Li, Jiao AU - Li J AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Luo, Jiadi AU - Luo J AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Chu, Shuzhou AU - Chu S AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Shi, Lei AU - Shi L AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Huang, Donghai AU - Huang D AD - Department of Otorhinolaryngology, Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Li, Jinghe AU - Li J AD - Department of Pathology, Basic Medical College of Central South University, Changsha, Hunan, China. FAU - Fan, Songqing AU - Fan S AD - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140828 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cell Cycle Proteins) RN - 0 (EIF4EBP1 protein, human) RN - 0 (Phosphoproteins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1) SB - IM MH - Adaptor Proteins, Signal Transducing/*metabolism MH - Adolescent MH - Adult MH - Aged MH - Carcinoma MH - Cell Cycle Proteins MH - China MH - Female MH - Humans MH - Male MH - Middle Aged MH - Nasopharyngeal Carcinoma MH - Nasopharyngeal Neoplasms/*metabolism/*pathology MH - Phosphoproteins/*metabolism MH - Phosphorylation MH - Prognosis MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism MH - Signal Transduction MH - Survival Analysis MH - TOR Serine-Threonine Kinases/metabolism MH - Young Adult PMC - PMC4148345 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/08/29 06:00 MHDA- 2015/11/18 06:00 PMCR- 2014/08/28 CRDT- 2014/08/29 06:00 PHST- 2014/06/07 00:00 [received] PHST- 2014/07/23 00:00 [accepted] PHST- 2014/08/29 06:00 [entrez] PHST- 2014/08/29 06:00 [pubmed] PHST- 2015/11/18 06:00 [medline] PHST- 2014/08/28 00:00 [pmc-release] AID - PONE-D-14-25490 [pii] AID - 10.1371/journal.pone.0106098 [doi] PST - epublish SO - PLoS One. 2014 Aug 28;9(8):e106098. doi: 10.1371/journal.pone.0106098. eCollection 2014.