Clinical associations between ASCT2 and p-mTOR in the pathogenesis and prognosis of epithelial ovarian cancer
Clinical associations between ASCT2 and p-mTOR in the pathogenesis and prognosis of epithelial ovarian cancer
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DOI：
10.3892/or.2018.6729
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发表时间：
2018-12-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Kunhua
中科院分区：
文献类型：
--
作者：
Guo, Huiming;Xu, Yu;Wang, Kunhua
丙氨酸丝氨酸半胱氨酸偏好转运蛋白2（ASCT 2;也称为SLC 1A 5）是一种重要的谷氨酰胺转运蛋白，它在肿瘤生长和进展中起着至关重要的作用。ASCT 2在许多类型的癌症中高度表达，但其在上皮性卵巢癌（EOC）中表达的病理学意义仍不清楚。雷帕霉素（mTOR）水平的机制目标在许多肿瘤类型中过高，包括卵巢癌。本研究的目的是阐明ASCT 2和磷酸化（p）-mTOR在EOC中的预后作用。采用逆转录-定量聚合酶链反应（RT-qPCR）和western blot检测正常卵巢组织、良性卵巢肿瘤、交界性卵巢肿瘤和EOC组织中ASCT 2和p-mTOR/mTOR的表达。采用免疫组化（IHC）法检测EOC患者中ASCT 2和p-mTOR的蛋白水平。此外，对EOC肿瘤切片进行Ki-67和分化簇34（CD 34）染色，以通过IHC评估增殖和微血管密度。RT-qPCR和western blot分析结果显示，ASCT 2和p-mTOR蛋白在EOC组织中的表达水平显著高于其他各组。104例EOC组织中ASCT 2的表达与国际妇产科联合会临床分期、病理分级、血清癌抗原125水平、Ki-67状态和CD 34状态等临床病理参数相关。Kaplan-Meier生存曲线分析显示ASCT 2和p-mTOR高表达是EOC患者预后不良的重要因素。上皮性卵巢癌中ASCT 2和p-mTOR的表达水平呈正相关（r=0.385，P
Alanine serine cysteine-preferring transporter 2 (ASCT2; also known as SLC1A5) is an important glutamine transporter, and it serves a crucial role in tumor growth and progression. ASCT2 is highly expressed in numerous types of cancer, but the pathological significance of its expression in epithelial ovarian cancer (EOC) remains unclear. The mechanistic target of rapamycin (mTOR) level is hyperelevated in a number of tumor types, including ovarian cancer. The aim of the present study was to elucidate the prognostic role of ASCT2 and phosphorylated (p)-mTOR in EOC. The levels of ASCT2 and p-mTOR/mTOR were detected in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and EOC tissues by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The protein levels of ASCT2 and p-mTOR in EOC patients were then detected by immunohistochemistry (IHC). Furthermore, EOC tumor sections were stained for Ki-67 and cluster of differentiation 34 (CD34) to assess proliferation and microvessel density by IHC. The results of RT-qPCR and western blot analysis demonstrated that ASCT2 and p-mTOR protein levels were significantly higher in EOC tissues compared with those in other groups. IHC analysis of 104 EOC tissues suggested that ASCT2 expression was associated with clinicopathological parameters, including International Federation of Gynecology and Obstetrics stage, pathological grade, serum cancer antigen 125 level, Ki-67 status and CD34 status. Kaplan-Meier survival curve analysis indicated that high expression of ASCT2 and p-mTOR were important factors predicting a poor prognosis for patients with EOC. The expression levels of ASCT2 and p-mTOR in EOC were positively correlated (r=0.385, P