Overexpression of P-4EBP1 Associates with P-eIF4E and Predicts Poor Prognosis for Non-small Cell Lung Cancer Patients with Resection

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Jun 23

PMID 35737644

Authors

Yaoxiang Tang

Jiadi Luo

Yang Yang

Sile Liu

Hongmei Zheng

Yuting Zhan

Songqing Fan

Qiuyuan Wen

Affiliations

Soon will be listed here.

Abstract

Eukaryotic initiation factor 4E (eIF4E) and its phosphorylated form (p-eIF4E) play a crucial role in the protein synthesis, both are under regulation of eIF4E-binding protein 1 (4EBP1) and mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). This study aims to explore the potential prognostic significance of p-4EBP1 and p-eIF4E in NSCLC patients. The expression of p-4EBP1 and p-eIF4E in NSCLC patients was detected by immunohistochemistry (IHC) staining in tissue microarrays (TMAs) containing 354 NSCLC and 53 non-cancerous lung tissues (Non-CLT). The overexpression percentage of p-4EBP1 and p-eIF4E in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) was significantly higher than that of Non-CLT. P-4EBP1 expression in patients with advanced clinical stage was higher than that in early stage. Expression of p-4EBP1 had a positive relationship with p-eIF4E expression both in lung SCC and ADC. NSCLC patients with high expression of p-4EBP1 and p-eIF4E alone or in combination had a lower survival rate than that of other phenotypes. For NSCLC patients, p-4EBP1 is an independent poor prognostic factor as well as clinical stage, LNM and pathological grade. Overexpression of p-4EBP1 and p-eIF4E might be novel prognostic marker for NSCLC, who possesses potential application value for NSCLC targeted therapy.

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References

Grzmil M, Huber R, Hess D, Frank S, Hynx D, Moncayo G . MNK1 pathway activity maintains protein synthesis in rapalog-treated gliomas. J Clin Invest. 2014; 124(2):742-54. PMC: 3904612. DOI: 10.1172/JCI70198. View

Wen Q, Wang W, Luo J, Chu S, Chen L, Xu L . CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating mitochondrial apoptotic pathway. Oncotarget. 2016; 7(19):27787-801. PMC: 5053688. DOI: 10.18632/oncotarget.8497. View

Lu Y, Yu S, Wang G, Ma Z, Fu X, Cao Y . Elevation of EIF4G1 promotes non-small cell lung cancer progression by activating mTOR signalling. J Cell Mol Med. 2021; 25(6):2994-3005. PMC: 7957198. DOI: 10.1111/jcmm.16340. View

Fan S, Ma J, Zhou J, Xiong W, Xiao B, Zhang W . Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis. Hum Pathol. 2006; 37(5):593-605. DOI: 10.1016/j.humpath.2006.01.010. View

Musa J, Orth M, Dallmayer M, Baldauf M, Pardo C, Rotblat B . Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1): a master regulator of mRNA translation involved in tumorigenesis. Oncogene. 2016; 35(36):4675-88. DOI: 10.1038/onc.2015.515. View

Dhillon A, Hagan S, Rath O, Kolch W . MAP kinase signalling pathways in cancer. Oncogene. 2007; 26(22):3279-90. DOI: 10.1038/sj.onc.1210421. View

Lin X, Huang Y, Sun Y, Tan X, Ouyang J, Zhao B . 4E-BP1 Phosphorylation Association with Poor Prognosis in Quantitative Phosphoproteomics of Portal Vein Tumor Thrombus Revealed that 4E-BP1Thr46 Phosphorylation is Associated with Poor Prognosis in HCC. Cancer Manag Res. 2020; 12:103-115. PMC: 6954833. DOI: 10.2147/CMAR.S230849. View

Fan S, Ramalingam S, Kauh J, Xu Z, Khuri F, Sun S . Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Cancer Biol Ther. 2009; 8(15):1463-9. PMC: 2804981. DOI: 10.4161/cbt.8.15.8960. View

Liu X, Xiang D, Xu C, Chai R . EIF3m promotes the malignant phenotype of lung adenocarcinoma by the up-regulation of oncogene CAPRIN1. Am J Cancer Res. 2021; 11(3):979-996. PMC: 7994172. View

10.

Proud C . Mnks, eIF4E phosphorylation and cancer. Biochim Biophys Acta. 2014; 1849(7):766-73. DOI: 10.1016/j.bbagrm.2014.10.003. View

11.

Alabdullah M, Ahmad D, Moseley P, Madhusudan S, Chan S, Rakha E . The mTOR downstream regulator (p-4EBP1) is a novel independent prognostic marker in ovarian cancer. J Obstet Gynaecol. 2019; 39(4):522-528. DOI: 10.1080/01443615.2018.1534091. View

12.

Travis W, Brambilla E, Nicholson A, Yatabe Y, Austin J, Beasley M . The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015; 10(9):1243-1260. DOI: 10.1097/JTO.0000000000000630. View

13.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

14.

Gantenbein N, Bernhart E, Anders I, Golob-Schwarzl N, Krassnig S, Wodlej C . Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression. Eur J Cancer. 2018; 101:165-180. DOI: 10.1016/j.ejca.2018.07.001. View

15.

Haghighat A, Mader S, Pause A, Sonenberg N . Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995; 14(22):5701-9. PMC: 394685. DOI: 10.1002/j.1460-2075.1995.tb00257.x. View

16.

Osmani L, Askin F, Gabrielson E, Li Q . Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin Cancer Biol. 2017; 52(Pt 1):103-109. PMC: 5970946. DOI: 10.1016/j.semcancer.2017.11.019. View

17.

Wang X, Yue P, Chan C, Ye K, Ueda T, Watanabe-Fukunaga R . Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation. Mol Cell Biol. 2007; 27(21):7405-13. PMC: 2169067. DOI: 10.1128/MCB.00760-07. View

18.

Hao P, Yu J, Ward R, Liu Y, Hao Q, An S . Eukaryotic translation initiation factors as promising targets in cancer therapy. Cell Commun Signal. 2020; 18(1):175. PMC: 7640403. DOI: 10.1186/s12964-020-00607-9. View

19.

Zheng J, Li J, Xu L, Xie G, Wen Q, Luo J . Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma. PLoS One. 2014; 9(2):e89220. PMC: 3925237. DOI: 10.1371/journal.pone.0089220. View

20.

Rojo F, Najera L, Lirola J, Jimenez J, Guzman M, Sabadell M . 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis. Clin Cancer Res. 2007; 13(1):81-9. DOI: 10.1158/1078-0432.CCR-06-1560. View