Low level of isocitrate dehydrogenase 1 predicts unfavorable postoperative outcomes in patients with clear cell renal cell carcinoma

BACKGROUND: The purpose of this study was to investigate the role of isocitrate dehydrogenase 1 (IDH1) expression on prognosis of patients with clear cell renal cell carcinoma (ccRCC) following nephrectomy. METHODS: We retrospectively enrolled 358 ccRCC patients undergoing nephrectomy in Renji Hospital. Clinicopathologic features, overall survival (OS) and recurrence-free survival (RFS) of ccRCC patents were all collected. IDH1 expression level was assessed by immunohistochemistry and its association with clinicopathologic features and outcomes were also evaluated. Kaplan-Meier method with the log-rank test was applied to compare survival curves. Multivariate cox regression models were applied to analyze the prognostic value of each factor on OS and RFS of ccRCC patients. Moreover, two nomograms with factors selected by multivariate analysis were constructed to evaluate the prognosis of ccRCC patients, and the calibration plots were built to assess the predictive accuracy of nomograms. RESULTS: Our data indicated that IDH1 expression level was down-regulated in ccRCC tissues, and it negatively correlated with tumor Fuhrman grade (p = 0.025). Low IDH1 expression was associated with worse OS and RFS for cccRCC patients (OS, p = 0.004; RFS, p = 0.03). In addition, IDH1 could significantly stratify patients’ OS and RFS in intermediate/high risk patients (UISS score ≥ 4) (p = 0.049 and p = 0.004, respectively). Furthermore, incorporating IDH1 with other prognostic factors could predict ccRCC patients’ OS and RFS (OS, c-index = 0.779; RFS, c-index = 0.798) and perform better than TNM and SSIGN system. CONCLUSIONS: Low IDH1 expression level might be an adverse prognostic biomarker for clinical outcomes of ccRCC patients, and two nomograms with IDH1 are potential effective prognostic models for ccRCC.