https://doi.org/10.4081/ejh.2021.3304
Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma
Submitted: 12 July 2021
Accepted: 11 October 2021
Published: 16 November 2021
Accepted: 11 October 2021
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The primary aim of this study was to examine the correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognostic significance in nasopharyngeal carcinoma (NPC). The study tissues were collected from 285 patients with NPC and normal mucosal tissues were obtained from 289 individuals with normal nasopharynxes. Immunohistochemical staining was used to detected the expression of the AKT, mTOR, and p70 ribosomal S6 kinase (P70S6K) proteins. Follow-up was performed for between 8 and 60 months. Spearman’s rank correlation analysis was performed to evaluate the correlation of the expression of the AKT, mTOR, and P70S6K proteins in NPC tissues. Kaplan-Meier curves were plotted to show the survival of patients with NPC. A Cox proportional hazards model was used to explore the independent risk factors for prognosis. The expression of the AKT, mTOR, and P70S6K proteins in NPC tissues was higher than that in healthy nasopharyngeal mucosal tissues, and was correlated with T-staging, N-staging, clinical stage, distant metastasis, and differentiation. The positive expression of the AKT, mTOR, and P70S6K proteins was higher in patients with stage III/IV NPC, low differentiation, and metastasis. The survival rates of patients with NPC with AKT-positive, mTOR-positive, and P70S6K-positive expression were considerably lower than those without the expression of these proteins. Distant metastasis and the overexpression of the AKT, mTOR, and P70S6 proteins were independent risk factors for the prognosis of patients with NPC. The results obtained from this study indicated an association between the AKT/mTOR signaling pathway and the progression of NPC. The upregulation of the AKT/mTOR pathway in patients with NPC is a predictor of poor prognosis.
Yang L, Tang Y, He Y, Wang Y, Lian Y, Xiong F, et al. High expression of LINC01420 indicates an unfavorable prognosis and modulates cell migration and invasion in nasopharyngeal carcinoma. J Cancer 2017;8:97-103.
DOI: https://doi.org/10.7150/jca.16819
Xu L, Fan S, Zhao J, Zhou P, Chu S, Luo J, et al. Increased expression of Cks1 protein is associated with lymph node metastasis and poor prognosis in nasopharyngeal carcinoma. Diagn Pathol 2017;12:2.
DOI: https://doi.org/10.1186/s13000-016-0589-9
Wei GB, Lu YY, Liao RW, Chen QS, Zhang KQ. Prognostic nutritional index predicts prognosis in patients with metastatic nasopharyngeal carcinoma. Onco Targets Ther 2016;9:5955-61.
DOI: https://doi.org/10.2147/OTT.S114382
Suarez C, Rodrigo JP, Rinaldo A, Langendijk JA, Shaha AR, Ferlito A. Current treatment options for recurrent nasopharyngeal cancer. Eur Arch Otorhinolaryngol 2010;267:1811-24.
DOI: https://doi.org/10.1007/s00405-010-1385-x
Chen J, Hu CF, Hou JH, Shao Q, Yan LX, Zhu XF, et al. Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma. J Transl Med 2010;8:30.
Zhou XM, Sun R, Luo DH, Sun J, Zhang MY, Wang MH, et al. Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway. Oncotarget 2016;7:13634-50.
DOI: https://doi.org/10.18632/oncotarget.7215
Lung ML, Cheung AK, Ko JM, Lung HL, Cheng Y, Dai W. The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma. Chin J Cancer 2014;33:556-68.
DOI: https://doi.org/10.5732/cjc.014.10170
Wang W, Wen Q, Xu L, Xie G, Li J, Luo J, et al. Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma. PLoS One 2014;9:e106098.
Wang KF, Yang H, Jiang WQ, Li S, Cai YC. Puquitinib mesylate (XC-302) induces autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway in nasopharyngeal cancer cells. Int J Mol Med 2015;36:1556-62.
DOI: https://doi.org/10.3892/ijmm.2015.2378
Jiang Z, Liu Y, Wang C. Oncogenic NanogP8 expression regulates cell proliferation and migration through the Akt/mTOR signaling pathway in human gastric cancer - SGC-7901cell line. Onco Targets Ther 2016;9:4859-66.
DOI: https://doi.org/10.2147/OTT.S97861
Feng S, Jin Y, Cui M, Zheng J. Lysine-specific demethylase 1 (LSD1) inhibitor S2101 induces autophagy via the AKT/mTOR pathway in SKOV3 ovarian cancer cells. Med Sci Monit 2016;22:4742-8.
DOI: https://doi.org/10.12659/MSM.898825
Populo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci 2012;13:1886-918.
DOI: https://doi.org/10.3390/ijms13021886
Guo Q, Lu T, Chen Y, Su Y, Zheng Y, Chen Z, et al. Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy. Sci Rep 2016;6:37576.
DOI: https://doi.org/10.1038/srep37576
Peng DJ, Wang J, Zhou JY, Wu GS. Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells. Biochem Biophys Res Commun 2010;394:600-5.
DOI: https://doi.org/10.1016/j.bbrc.2010.03.029
Wu D, Cheng J, Sun G, Wu S, Li M, Gao Z, et al. p70S6K promotes IL-6-induced epithelial-mesenchymal transition and metastasis of head and neck squamous cell carcinoma. Oncotarget 2016;7:36539-50.
DOI: https://doi.org/10.18632/oncotarget.9282
Chang SL, Lee SW, Yang SF, Chien CC, Chan TC, Chen TJ, et al. Expression and prognostic utility of SSX2IP in patients with nasopharyngeal carcinoma. APMIS 2020;128:287-97.
DOI: https://doi.org/10.1111/apm.13023
Clark C, Shah S, Herman-Ferdinandez L, Ekshyyan O, Abreo F, Rong X, et al. Teasing out the best molecular marker in the AKT/mTOR pathway in head and neck squamous cell cancer patients. Laryngoscope 2010;120:1159-65.
Huang WB, Chan JYW, Liu DL. Human papillomavirus and World Health Organization type III nasopharyngeal carcinoma: Multicenter study from an endemic area in Southern China. Cancer 2018;124:530-6.
DOI: https://doi.org/10.1002/cncr.31031
Kalogera-Fountzila A, Karanikolas D, Katodritis N, Samantas E, Sarafopoulos A, Ikonomou I, et al. Prognostic factors and significance of the revised 6th edition of the AJCC classification in patients with locally advanced nasopharyngeal carcinoma. Strahlenther Onkol 2006;182:458-66.
DOI: https://doi.org/10.1007/s00066-006-1538-4
Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer 1993;72:2979-85.
DOI: https://doi.org/10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X
Kim TJ, Lee YS, Kang JH, Kim YS, Kang CS. Prognostic significance of expression of VEGF and Cox-2 in nasopharyngeal carcinoma and its association with expression of C-erbB2 and EGFR. J Surg Oncol 2011;103:46-52.
DOI: https://doi.org/10.1002/jso.21767
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
DOI: https://doi.org/10.3322/caac.20107
Korkolopoulou P, Levidou G, Trigka EA, Prekete N, Karlou M, Thymara I, et al. A comprehensive immunohistochemical and molecular approach to the PI3K/AKT/mTOR (phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene/mammalian target of rapamycin) pathway in bladder urothelial carcinoma. BJU Int 2012;110:E1237-48.
DOI: https://doi.org/10.1111/j.1464-410X.2012.11569.x
Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 2005;16:797-803.
DOI: https://doi.org/10.1097/01.cad.0000173476.67239.3b
Wang G, Liu M, Wang H, Yu S, Jiang Z, Sun J, et al. Centrosomal protein of 55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway. J Cancer 2016;7:1431-40.
DOI: https://doi.org/10.7150/jca.15497
Qin J, Ji J, Deng R, Tang J, Yang F, Feng GK, et al. DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma cancer stem-like cells by downregulating Sox2. Oncotarget 2015;6:6944-58.
DOI: https://doi.org/10.18632/oncotarget.3128
Costa C, Pereira S, Lima L, Peixoto A, Fernandes E, Neves D, et al. Abnormal protein glycosylation and activated PI3K/Akt/mTOR pathway: Role in bladder cancer prognosis and targeted therapeutics. PLoS One 2015;10:e141253.
DOI: https://doi.org/10.1371/journal.pone.0141253
Zhang X, Shi H, Tang H, Fang Z, Wang J, Cui S. miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway. Int J Mol Med 2015;35:1301-8.
DOI: https://doi.org/10.3892/ijmm.2015.2126
Chang L, Graham PH, Ni J, Hao J, Bucci J, Cozzi PJ, et al. Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol 2015;96:507-17.
DOI: https://doi.org/10.1016/j.critrevonc.2015.07.005
Toker A. Achieving specificity in Akt signaling in cancer. Adv Biol Regul 2012;52:78-87.
DOI: https://doi.org/10.1016/j.advenzreg.2011.09.020
Clark C, Shah S, Herman-Ferdinandez L, Ekshyyan O, Abreo F, Rong X, et al. Teasing out the best molecular marker in the AKT/mTOR pathway in head and neck squamous cell cancer patients. Laryngoscope 2010;120:1159-65.
DOI: https://doi.org/10.1002/lary.20917
Li HF, Kim JS, Waldman T. Radiation-induced Akt activation modulates radio resistance in human glioblastoma cells. Curr Mol Med 2009;4:43.
DOI: https://doi.org/10.1186/1748-717X-4-43
Li Q, Ni W, Deng Z, Liu M, She L, Xie Q. Targeting nasopharyngeal carcinoma by artesunate through inhibiting Akt/mTOR and inducing oxidative stress. Fundam Clin Pharmacol 2017;31:301-10.
DOI: https://doi.org/10.1111/fcp.12266
Xu ZZ, Xia ZG, Wang AH, Wang WF, Liu ZY, Chen LY, et al. Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma: clinical significance and inhibitory effect of rituximab. Ann Hematol 2013;92:1351-8.
DOI: https://doi.org/10.1007/s00277-013-1770-9
Chen J, Hu CF, Hou JH, Shao Q, Yan LX, Zhu XF, et al. Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma. J Transl Med 2010;8:30.
DOI: https://doi.org/10.1186/1479-5876-8-30
Zhang M, Zhou X, Zhou K. Resveratrol inhibits human nasopharyngeal carcinoma cell growth via blocking pAkt/p70S6K signaling pathways. Int J Mol Med 2013;31:621-7.
DOI: https://doi.org/10.3892/ijmm.2013.1237
Wang W, Wen Q, Xu L, Xie G, Li J, Luo J, et al. Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma. PLoS One 2014;9:e106098.
DOI: https://doi.org/10.1371/journal.pone.0106098
Garcia-Carracedo D, Villaronga MA, Alvarez-Teijeiro S, Hermida-Prado F, Santamaria I, Allonca E, et al. Impact of PI3K/AKT/mTOR pathway activation on the prognosis of patients with head and neck squamous cell carcinomas. Oncotarget 2016;7:29780-93.
DOI: https://doi.org/10.18632/oncotarget.8957
Ma BB, Lui VW, Hui EP, Lau CP, Ho K, Ng MH, et al. The activity of mTOR inhibitor RAD001 (everolimus) in nasopharyngeal carcinoma and cisplatin-resistant cell lines. Invest New Drugs 2010;28:413-20.
DOI: https://doi.org/10.1007/s10637-009-9269-x
Magnuson B, Ekim B, Fingar DC. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 2012;441:1-21.
DOI: https://doi.org/10.1042/BJ20110892
Liu L, Li F, Cardelli JA, Martin KA, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 2006;25:7029-40.
DOI: https://doi.org/10.1038/sj.onc.1209691
Zhou H, Huang S. Role of mTOR signaling in tumor cell motility, invasion and metastasis. Curr Protein Pept Sci 2011;12:30-42.
DOI: https://doi.org/10.2174/138920311795659407
How to Cite
Wang, Y., Sun, J., & Yao, N. (2021). Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma. European Journal of Histochemistry, 65(4). https://doi.org/10.4081/ejh.2021.3304
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