Clinical associations between ASCT2 and p‑mTOR in the pathogenesis and prognosis of epithelial ovarian cancer

Guo,Huiming; Xu,Yu; Wang,Feng; Shen,Zongwen; Tuo,Xiaoyu; Qian,Hong; Wang,Huawe; Wang,Kunhua

doi:10.3892/or.2018.6729

Clinical associations between ASCT2 and p‑mTOR in the pathogenesis and prognosis of epithelial ovarian cancer

Authors:
- Huiming Guo
- Yu Xu
- Feng Wang
- Zongwen Shen
- Xiaoyu Tuo
- Hong Qian
- Huawe Wang
- Kunhua Wang
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Affiliations: Department of Gynecology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Gynecology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Yunnan Engineering Technology Center of Diagnosis and Treatment of Digestive Diseases, Kunming, Yunnan 650032, P.R. China
Published online on: September 24, 2018 https://doi.org/10.3892/or.2018.6729
Pages: 3725-3733

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Abstract

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<0.001). This positive correlation between ASCT2 and p‑mTOR indicates that they have a synergistic effect on the growth and development of early EOC. The combined detection of ASCT2 and p‑mTOR may serve as a potential marker to inform diagnosis, postoperative follow‑up requirements and targeted therapy options for patients with early‑stage EOC, but not for terminal‑stage patients.

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