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

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.

Figure 1. SLC1A5 expression in clear-cell renal cell carcinoma (ccRCC) tissues and dichotomization of patients based on the cutoff of H-score.

(a) Representative immunohistochemical (IHC) images of ccRCC tissues with differential expression level of SLC1A5. Case 1 (H-score) = 0 × 69 (%) + 1 × 26 (%) + 2 × 5 (%) + 3 × 0 (%) = 36; Case 2 (H-score) = 0 × 22 (%) + 1 × 51 (%) + 2 × 27 (%) + 3 × 0 (%) = 105; Case 3 (H-score) = 0 × 8 (%) + 1 × 40 (%) + 2 × 32 (%) + 3 × 20 (%) = 164; Case 4 (H-score) = 0 × 0 (%) + 1 × 5 (%) + 2 × 41 (%) + 3 × 54 (%) = 249. Scale bar: 50 μm (original magnification × 200, × 400). (b) Dichotomization of patients based on the cutoff of H-score selected via “minimum P value” approach.

Figure 2. Overall survival (OS) and Recurrence-free survival (RFS) analysis of patients with ccRCC based on dichotomized SLC1A5 expression.

(a) Kaplan-Meier analysis of OS (n = 187). (b) Kaplan-Meier analysis of RFS (n = 179). Eight patients with tumor metastasis at the time of surgical operation were excluded from the RFS analysis as indicated by the end point of RFS. P value was calculated by log-rank test.

Figure 3. Nomogram and calibration plot for prediction of OS in patients with ccRCC.

Postoperative prognostic nomogram of patients with ccRCC (a). The calibration plots for predicting survival at 3 years (b), 5 years (c) and 10 years (d).

Figure 4. Kaplan–Meier curves of overall survival based on risk score calculated by nomogram.

Statistical differences between each two subgroups were assessed by log-rank test.

Figure 5. Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis of nomogram-based model.

(a) Kaplan-Meier analysis of patients according to stages of nomogram-based model. P value was calculated by log-rank test. (b) ROC analysis of the sensitivity and specificity for the prediction of OS of TNM staging system and nomogram-based model.