Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer |
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Authors: | No Jae Hong Jeon Yong-Tark Park In-Ae Kim Yong-Beom Kim Jae Weon Park Noh-Hyun Kang Soon-Beom Han Jae Yong Lim Jeong Mook Song Yong-Sang |
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Affiliation: | a Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Koreab Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Koreac Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Koread Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Koreae Major in Biomodulation, World Class University, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea |
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Abstract: | ObjectiveActivation of the mammalian target of rapamycin (mTOR) pathway enhances cell survival and growth by regulating the efficiency of protein translation. This study was conducted to evaluate the association of activated mTOR signaling molecules with the clinicopathologic characteristics in epithelial ovarian cancer.MethodsImmunohistochemical staining with antibodies against p-4EBP1, p-mTOR, and p-p70S6K were performed on specimens of 103 patients with ovarian cancer. Tumors were classified as chemoresistant in cases where time to recurrence after the end of chemotherapy was shorter than 6 months.ResultsExpressions of p-mTOR, p-4EBP1, and p-p70S6K were detected in 47.6%, 85.4%, and 64.1% of all patients, respectively. p-4EBP1 overexpression was associated with advanced stage (p = 0.04), histologic grade (p < 0.01), residual mass (p < 0.01), shorter disease-free survival rate (p = 0.01) and chemoresistance (p = 0.02). p-p70S6K was associated with residual mass with marginal significance (p = 0.06). p-4EBP1 expression was correlated with p-p70S6K expression (r = 0.42, p < 0.01), whereas p-mTOR was not associated with expression of its downstream effectors or prognostic factors.ConclusionsOur findings suggest that p-4EBP1 expression was associated with poor prognostic factors of ovarian cancer and that p-4EBP1 overexpression may be a prognostic biomarker of ovarian cancer. |
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Keywords: | p-mTOR p-4EBP1 p-p70S6K Epithelial ovarian cancer |
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