Abstract
Astrocyte elevated gene-1 (AEG-1), a novel tumor-associated gene, was found overexpressed in many tumors. Therefore, our purpose is to estimate whether AEG-1 overexpression is a novel predictor of prognostic marker in metastatic ovarian tumors. Immunohistochemistry was used to estimate AEG-1 overexpression in metastatic ovarian tumors from 102 samples. The association between AEG-1 expression and prognosis was estimated by univariate and multivariate survival analyses with Cox regression. The log-rank test was used to identify any differences in the prognosis between the two groups. The median overall and progression-free survival rates of patients with tumors from gastrointestinal tract origin were 0.97 and 0.51 years, respectively. Similarly, survival rates of patients with tumors of breast origin were 2.68 and 1.96 years (P < 0.0001). Of 102 patients, 77 had high expression, and AEG-1 overexpression had a significant link of prognosis in metastatic ovarian patients (P < 0.01). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the tumors from gastrointestinal tract primary malignancies. It is suggested that AEG-1 overexpression might be an independent prognostic marker of metastatic ovarian tumors.
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References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.
Yada-Hashimoto N, Yamamoto T, Kamiura S, et al. Metastatic ovarian tumors: a review of 64 cases. Gynecol Oncol. 2003;89:314–7.
Kondi-Pafiti A, Kairi-Vasilatou E, Iavazzo C, et al. Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases. Arch Gynecol Obstet. 2011;284:1283–8.
Su ZZ, Kang DC, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RasH. Oncogene. 2002;21:3592–602.
Brown DM, Ruoslahti E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 2004;5:365–74.
Meng X, Zhu D, Yang S, et al. Cytoplasmic metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein. J Biol Chem. 2012;287(7):4485–91.
Thirkettle HJ, Mills IG, Whitaker HC, et al. Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene. 2009;28(41):3663–70.
Yoo BK, Emdad L, Sarkar D, et al. Astrocyte elevated gene-1 (AEG-1): a multifunctional regulator of normal and abnormal physiology. Pharmacol Ther. 2011;130(1):1–8.
Emdad L, Lee SG, Fisher PB, et al. Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis. Proc Natl Acad Sci U S A. 2009;106(50):21300–5.
Ash SC, Yang DQ, Britt DE. LYRIC/AEG-1 overexpression modulates BCCIP alpha protein levels in prostate tumor cells. Biochem Biophys Res Commun. 2008;371(2):333–8.
Lee HJ, Jung DB, Kim SH, et al. Inhibition of hypoxia inducible factor alpha and astrocyte-elevated gene-1 mediates cryptotanshinone exerted antitumor activity in hypoxic PC-3 cells. Evid Based Complement Alternat Med. 2012;2012:1–13.
He XX, Chang Y, Meng FY, Wang MY, Xie QH, Tang F, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357–69.
Kang DC, Su ZZ, Sarkar D, et al. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 2005;353:8–15.
Noch E, Bookland M, Khalili K. Astrocyte-elevated gene-1 (AEG-1) induction by hypoxia and glucose deprivation in glioblastoma. Cancer Biol Ther. 2011;11(1):32–9.
Zheng JS, Li C, Wu X, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumor Biol. 2013. doi:10.1007/s13277-013-1300-3.
Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.
Li C, Song H, Geng J, et al. AEG-1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. Int J Gynecol Cancer. 2011;21(4):602–8.
Erdem H, Yildirim U, Uzunlar AK, Cam K, Tekin A, Kayikci MA, et al. Relationship among expression of basic-fibroblast growth factor, MTDH/Astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9, and COX-2 markers with prognostic factors in prostate carcinomas. Niger J Clin Pract. 2013;16(4):418–23.
Meng F, Song H, Lou G, et al. Clinical significance of astrocyte elevated gene-1 expression in human epithelial ovarian carcinoma. Int J Gynecol Pathol. 2011;30(2):145–50.
Sarkar D. AEG-1/MTDH/LYRIC in liver cancer. Adv Cancer Res. 2013;120:193–221.
Sarkar D, Park ES, Fisher PB, et al. Molecular basis of nuclear factor-kappaB activation by astrocyte elevated gene-1. Cancer Res. 2008;68(5):1478–84.
Emdad L, Sarkar D, Fisher PB, et al. Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Cancer Res. 2006;66(3):1509–16.
Wang YP, Liu IJ, Chiang CP, Wu HC. Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1. Mol Cancer. 2013;12(1):109.
Li C, Song H, Geng J, et al. Elevated expression of AEG-1 is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III-IV serous ovarian carcinoma. Histopathology. 2012;60(6):953–63.
Li C, Song H, Geng J, et al. Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinicopathological characteristics in triple-negative breast cancer [J]. J Surg Oncol. 2011;103(2):184–92.
Song H, Li C, Geng J, et al. Prognostic significance of AEG-1 expression in colorectal carcinoma. Int J Color Dis. 2010;25(10):1201–9.
Noch EK, Khalili K. The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease. Adv Cancer Res. 2013;120:159–92.
Meng X, Thiel KW, Leslie KK. Drug resistance mediated by AEG-1/MTDH/LYRIC. Adv Cancer Res. 2013;120:135–57.
Wan L, Kang Y. Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Adv Cancer Res. 2013;120:113–34.
Emdad L, Das SK, Dasgupta S, Hu B, Sarkar D, Fisher PB. AEG-1/MTDH/LYRIC: signaling pathways, downstream genes, interacting proteins, and regulation of tumor angiogenesis. Adv Cancer Res. 2013;120:75–111.
Lee SG, Kang DC, DeSalle R, Sarkar D, Fisher PB. AEG-1/MTDH/LYRIC, the beginning: initial cloning, structure, expression profile, and regulation of expression. Adv Cancer Res. 2013;120:1–38.
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This work is supported by the National Natural Science Foundation of China (no. 81372785) and the Key Project of Natural Science Foundation of Heilongjiang Province (no. 41400453-8-13146).
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Li, C., Chen, K., Cai, J. et al. Astrocyte elevated gene-1: a novel independent prognostic biomarker for metastatic ovarian tumors. Tumor Biol. 35, 3079–3085 (2014). https://doi.org/10.1007/s13277-013-1400-0
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DOI: https://doi.org/10.1007/s13277-013-1400-0