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A Promising Predictor of the Efficacy of Endocrine Therapy for Breast Cancer:14-3-3-zeta |
Shunchao Yan1*, Xin Jiao2, Na Li1, Yangfan Du1 |
1. Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, China; 2. Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang 110044, China |
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Abstract Objective 14-3-3-zeta protein has been found to be associated with survival signaling in cancer. However, prognostic value and the predictive effect of its gene expression for determining the efficacy of endocrine therapy in breast cancer are unclear. Methods The differential 14-3-3-zeta gene expression between cancer and normal tissue was assayed using ONCOMINE database analysis. The correlation between 14-3-3-zeta gene and proliferative/metastasis-associated genes was analyzed using Breast Cancer Gene-Expression Miner v4.1 (bc-GenExMiner v4.1). The prognostic value of its expression in breast cancer was analyzed using bc-GenExMiner v4.1 and Kaplan-Meier Plotter. Results The 14-3-3-zeta gene expression was elevated in breast cancer tissue compared with normal breast tissue,which was higher in invasive ductal breast cancer than in ductal breast cancer in situ. It was also positively correlated with the degree of malignancy and the clinical stage of breast cancer and with some proliferative genes. A high level of 14-3-3-zeta expression was predictive of shorter relapse-free survival (RFS) in ER-positive but not ER-negative breast cancer. Further analysis showed the association of high 14-3-3-zeta expression and a shorter RFS in endocrine therapy or tamoxifen-only-treated population, regardless of whether chemotherapy had been used. Conclusion 14-3-3-zeta gene expression is upregulated and associated with a relatively high degree of malignancy and late clinical stage in breast cancer. It is a promising prognostic factor for ER-positive breast cancer and a predictor of the efficacy of endocrine therapy.
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Fund:Science and Technology Foundation of Liaoning Province: 20170540995; Science and Technology Foundation of Shenyang City: RC170545; the National Science Foundation of China: 81302313; Talent Project of Shengjing Hospital of China Medical University: 345. |
Corresponding Authors:
Shunchao Yan, Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, China. E-mail address: yan50@illinois.edu
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[1] Chen W, Sun K, Zheng R,et al.Cancer incidence and mortality in China, 2014[J]. Chinese Journal of Cancer Research, 2018,30:1-12. [2] Bray F, Ferlay J, Soerjomataram I,et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018,68:394-424. [3] Yersal O, Barutca S. Biological subtypes of breast cancer. Prognostic and therapeutic implications[J]. World J Clin Oncol,2014,5:412-24. [4] Clark GM, Osborne CK, McGuire WL. Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer[J]. J Clin Oncol,1984,2:1102-1109. [5] Basile D,Cinausero M,Iacono D,et al.Androgen receptor in estrogen receptor positive breast cancer: Beyond expression[J]. Cancer Treatment Reviews,2017,61:15-22. [6] Aitken A. 14-3-3 proteins: a historic overview[J]. Semin Cancer Biol,2006,16:162-172. [7] Cau Y, Valensin D, Mori M,et al.Structure, function, involvement in diseases and targeting of 14-3-3 proteins: An update[J]. Current Medicinal Chemistry,2018,25:5-21. [8] Aitken A, Jones D, Soneji Y,et al.14-3-3 proteins: biological function and domain structure[J]. Biochem Soc Trans,1995,23:605-611. [9] Joshi S, Yang J, Wang Q,et al.14-3-3ζ loss impedes oncogene-induced mammary tumorigenesis and metastasis by attenuating oncogenic signaling[J]. American Journal of Cancer Research,2017,7:1654-1664. [10] Liu ZR, Song Y, Wan LH,et al.Over-expression of miR-451a can enhance the sensitivity of breast cancer cells to tamoxifen by regulating 14-3-3ζ, estrogen receptor α, and autophagy[J]. Life Sci,2016,149:104-113. [11] Thistle JE, Hellberg Y, Mortensen K,et al.The effect of 14-3-3ζ expression on tamoxifen resistance and breast cancer recurrence: a Danish population-based study[J]. Breast Cancer Research and Treatment,2017,165:633-643. [12] Jézéquel P, Campone M, Gouraud W,et al.bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer[J]. Breast Cancer Res Treat, 2012,131:765-775. [13] Jézéquel P, Frénel JS, Campion L,et al.bc-GenExMiner 3.0: new mining module computes breast cancer gene-expression correlation analyses[J]. Database (Oxford), 2013,2013:bas060. [14] Lanczky A, Nagy A, Bottai G,et al.miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2,178 breast cancer patients[J]. Breast Cancer Res Treat, 2016,160:439-446. [15] Ma XJ, Dahiya S, Richardson E,et al.Gene expression profiling of the tumor microenvironment during breast cancer progression[J]. Breast Cancer Research, 2009,11:R7. [16] Radvanyi L, Singh-Sandhu D, Gallichan S,et al.The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer[J]. Proc Natl Acad Sci USA,2005,102:11005-11010. [17] Lee JK, Havaleshko DM, Cho H,et al.A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery[J]. Proc Natl Acad Sci USA,2007,104:13086-13091. [18] Toss M, Miligy I, Thompson AM,et al.Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: Critical review[J]. The Breast,2017,35:151-156. [19] Visser LL, Elshof LE, Schaapveld M,et al.Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ-A nested case-control study[J]. Clin Cancer Res,2018,24:3593-3601. [20] Croce CM. Oncogenes and cancer[J]. New England Journal of Medicine,2008,358:502-511. [21] Hussain SP, Harris CC. Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes[J]. Cancer Research,1998,58:4023-4037. [22] Saadatmand S, Bretveld R, Siesling S,et al.Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173797 patients[J]. BMJ,2015,351:h4901. [23] Pan H, Gray R, Braybrooke J,et al.EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years[J]. N Engl J Med,2017,377:1836-1846. [24] Mosly D, Turnbull A, Sims A,et al.Predictive markers of endocrine response in breast cancer[J]. World Journal of Experimental Medicine,2018,8: 1-7. [25] Martin M, Brase JC, Ruiz A,et al.Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study[J]. Breast Cancer Res Treat,2016,156:81-89. [26] Martin M, Brase JC, Calvo L,et al.Clinical validation of the EndoPredict test in node-positive, chemotherapy-treated ER+/HER2 breast cancer patients: results from the GEICAM 9906 trial[J]. Breast Cancer Research,2014,16:R38. [27] Fitzal F, Filipits M, Rudas M,et al.The genomic expression test EndoPredict is a prognostic tool for identifying risk of local recurrence in postmenopausal endocrine receptor-positive, her2neu-negative breast cancer patients randomised within the prospective ABCSG 8 tria[J].British Journal of Cancer,2015,112:1405-1410. [28] Peethambaram PP, Hoskin TL, Day CN,et al.Use of 21-gene recurrence score assay to individualize adjuvant chemotherapy recommendations in ER+/HER2- node positive breast cancer-A National Cancer Database study[J].NPJ Breast Cancer,2017,3:41. [29] Loncaster J, Armstrong A, Howell S,et al.Impact of Oncotype DX breast Recurrence Score testing on adjuvant chemotherapy use in early breast cancer: Real world experience in Greater Manchester, UK[J]. Eur J Surg Oncol,2017,43:931-937. [30] Bergamaschi A, Frasor J, Borgen K,et al.14-3-3ζ as a predictor of early time to recurrence and distant metastasis in hormone receptor-positive and-negative breast cancers[J]. Breast Cancer Research and Treatment, 2013,137:689-696. |
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