Expression of a-Tocopherol-Associated protein (TAP) is associated with clinical outcome in breast cancer patients
Tóm tắt
The role of vitamin E in breast cancer prevention and treatment has been widely investigated, and the different tocopherols that comprise this nutrient have been shown to have divergent associations with cancer outcome. Our previous studies have shown that α-Tocopherol-associated protein (TAP), a vitamin E binding protein, may function as a tumor suppressor-like factor in breast carcinogenesis. The current study addresses the association of TAP expression with breast cancer clinical outcomes. Immunohistochemical stain for TAP was applied to a tissue microarray from a breast cancer cohort consisting of 271 patients with a median follow-up time of 5.2 years. The expression of TAP in tumor cells was compared with patient’s clinical outcome at 5 years after diagnosis. The potential role of TAP in predicting outcome was also assessed in clinically relevant subsets of the cohort. In addition, we compared TAP expression and Oncotype DX scores in an independent breast cancer cohort consisting of 71 cases. We demonstrate that the expression of TAP was differentially expressed within the breast cancer cohort, and that ER+/PR ± tumors were more likely to exhibit TAP expression. TAP expression was associated with an overall lower recurrence rate and a better 5-year survival rate. This association was primarily in patients with ER+ tumors; exploratory analysis showed that this association was strongest in patients with node-positive tumors and was independent of stage and treatment with chemotherapy. TAP expression in ER/PR negative or triple negative tumors had no association with clinical outcome. In addition, we did not observe an association between TAP expression and Oncotype DX recurrence score. The significant positive association we found for α-Tocopherol-associated protein with outcome in breast cancer may help to better define and explain studies addressing α-tocopherol’s association with cancer risk and outcome. Additionally, further studies to validate and extend these findings may allow TAP to serve as a breast-specific prognostic marker in breast cancer patients, especially in those patients with ER+ tumors.
Tài liệu tham khảo
Wada S. Cancer preventive effects of vitamin E, vol. 13, 2011/04/07 edn.
Kline K, Yu W, Sanders BG. Vitamin E and breast cancer. J Nutr. 2004;134(12 Suppl):3458S–62S.
Ju J, Picinich SC, Yang Z, Zhao Y, Suh N, Kong AN, et al. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis. 2010;31(4):533–42.
Klein EA, Thompson Jr IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549–56.
Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294(1):56–65.
Zimmer S, Stocker A, Sarbolouki MN, Spycher SE, Sassoon J, Azzi A. A novel human tocopherol-associated protein: cloning, in vitro expression, and characterization. J Biol Chem. 2000;275(33):25672–80.
Ni J, Wen X, Yao J, Chang HC, Yin Y, Zhang M, et al. Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res. 2005;65(21):9807–16.
Wang X, Ni J, Hsu CL, Johnykutty S, Tang P, Ho YS, et al. Reduced expression of tocopherol-associated protein (TAP/Sec14L2) in human breast cancer. Cancer Invest. 2009;27(10):971–7.
Johnykutty S, Tang P, Zhao H, Hicks DG, Yeh S, Wang X. Dual expression of alpha-tocopherol-associated protein and estrogen receptor in normal/benign human breast luminal cells and the downregulation of alpha-tocopherol-associated protein in estrogen-receptor-positive breast carcinomas. Mod Pathol. 2009;22(6):770–5.
Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, et al. Alteration of alpha-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Food Chem. 2013;138(2–3):1015–21.
Reyal F, van Vliet MH, Armstrong NJ, Horlings HM, de Visser KE, Kok M, et al. A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer. Breast Cancer Res. 2008;10(6):R93.
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.
Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.
Teschendorff AE, Naderi A, Barbosa-Morais NL, Pinder SE, Ellis IO, Aparicio S, et al. A consensus prognostic gene expression classifier for ER positive breast cancer. Genome Biol. 2006;7(10):R101.
van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.
Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365(9460):671–9.
Ring BZ, Seitz RS, Beck R, Shasteen WJ, Tarr SM, Cheang MC, et al. Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(19):3039–47.
Anderson K, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K. Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA. Cancer Res. 2004;64(12):4263–9.
Malafa MP, Neitzel LT. Vitamin E succinate promotes breast cancer tumor dormancy. J Surg Res. 2000;93(1):163–70.
Neuzil J, Weber T, Gellert N, Weber C. Selective cancer cell killing by alpha-tocopheryl succinate. Br J Cancer. 2001;84(1):87–9.
Yu W, Simmons-Menchaca M, Gapor A, Sanders BG, Kline K. Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr Cancer. 1999;33(1):26–32.
Hamilton A, Piccart M. The contribution of molecular markers to the prediction of response in the treatment of breast cancer: a review of the literature on HER-2, p53 and BCL-2. Ann Oncol. 2000;11(6):647–63.
Stratton J, Godwin M. The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis. Fam Pract. 2011;28(3):243–52.
Lu G, Xiao H, Li GX, Picinich SC, Chen YK, Liu A, et al. A gamma-tocopherol-rich mixture of tocopherols inhibits chemically induced lung tumorigenesis in A/J mice and xenograft tumor growth. Carcinogenesis. 2010;31(4):687–94.