High expression of Solute Carrier Family 1, member 5 (SLC1A5) is associated with poor prognosis in clear-cell renal cell carcinoma.

Le Xu,Yidong Liu,Huimin An,Weijuan Zhang,Jiejie Xu,Yu Zhu,Yuan Chang,Liu Yang

doi:10.1038/srep16954

Abstract

Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors on overall survival (OS). A nomogram was then constructed on the basis of the independent prognosticators identified on multivariate analysis. The predictive ability of the models was compared using Receiver operating characteristic (ROC) analysis. Our data indicated that high expression of SLC1A5 was significantly associated with advanced TNM stage, higher Fuhrman grade and shorter OS in ccRCC patients. Multivariate analysis confirmed that SLC1A5 was an independent prognosticator for OS. A nomogram integrating SLC1A5 and other independent prognosticators was constructed, which showed a better prognostic value for OS than TNM staging system. In conclusion, high SLC1A5 expression is an independent predictor of adverse clinical outcome in ccRCC patients after surgery.

Highlights

Renal cell carcinoma (RCC) represents 2–3% of all adult cancers
To investigate whether the expression pattern of SLC1A5 is altered during tumorigenesis of clear-cell renal cell carcinoma (ccRCC), we evaluated SLC1A5 expression levels in normal kidney tissues (n = 3 ), ccRCC tumor tissues (n = 1 0) and corresponding peri-tumor tissues (n = 10) by quantitative real-time PCR (qRT-PCR) analysis
The H-score of SLC1A5 expression ranged from 9 to 255, According to the “minimum P value” approach conducted by X-tile, 149 was determined as the cutoff to dichotomize the patients into SLC1A5 low group and SLC1A5 high group (Fig. 1b)

Summary

Introduction

Renal cell carcinoma (RCC) represents 2–3% of all adult cancers. Annually, it afflicts approximately 209,000 people and causes nearly 102,0 00 deaths around the world[1]. Pyrimidine synthesis, glutamine is converted to glutamate, which is the main nitrogen donor for the synthesis of nonessential amino acids[5]. Besides being utilized in anabolic metabolism, the exported glutamine serves as stimuli for the uptake of essential amino acids, which directly activates mTORC1 and protein synthesis[8]. Solute Carrier Family 1, member 5 (SLC1A5), named as ASCT2, belongs to system ASC and performs as a high-affinity glutamine transporter in cancer cells[11]. Consistent with the functions exerted by glutamine, SLC1A5 is profoundly involved in uptake of essential amino acids, activation of mTORC1 and glutamine-dependent tumor cell survival and growth[8]. SLC1A5 has been regarded as an indispensable “switch” of glutamine metabolism and to be a critical regulator for cancer development[12]. A nomogram integrating SLC1A5 expression and pathologic variables was established to help predict prognosis and guide management for ccRCC patients after surgery

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