Improved patient stratification is a challenge in adjuvant clear-cell renal cell carcinoma (ccRCC) trials. Long non-coding RNAs (lncRNAs) are genome-wide regulators with potent prognostic value. We aimed to predict risk of ccRCC recurrence based on lncRNA expression from two independent cohorts.
Identification of prognostic lncRNAs was performed in a training set of 351 samples of localized ccRCC from the Cancer Genome Atlas, using Cox regression based on disease-free (DFS) and overall survival. Functional annotation of differentially expressed genes according to lncRNA expression was performed. The validation cohort included 167 localized ccRCC patients. Gene expression was studied by qRT-PCR. Kaplan-Meier estimators and Cox regression models were used for survival and multivariate analyses. Primary endpoint was DFS.
MFI2-AS1 was best candidate lncRNA in the developmental study. Its expression was associated with immune response genes expression. In the validation cohort, MFI2-AS1 expression was associated with shorter DFS (Hazard Ratio (HR) for relapse 3·5, p = 0·0001), independently from Leibovich recurrence classification and grade. Combined with Leibovich classification, MFI2-AS1 status improved prediction of recurrence, with a C-index of 0·70 compared to 0·67 for MFI2-AS1 alone and 0·66 for Leibovich classification alone. In patients with aggressive tumors (Leibovich ≥ 5), MFI2-AS1 expression was associated with a dramatically increased risk or relapse (HR 12·16, p
MFI2-AS1 is a potent predictor of recurrence in localized ccRCC. Combined with historical classifications, it provides a highly accurate patient stratification that may be useful in adjuvant settings.
Clinical trial identification
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Gabriel G Malouf, MD, PhD. Fondation Avec & Hôpital Salpêtrière, Department of Medical Oncology, Paris, France
N. Tannir: Honoraria and consulting: Bristol-Myers Squib, Exelixis, Nektar, Novartis, Pfizer, Argos, Calithera. Research funding: Bristol-Myers Squib, Exelixis, Epizyme, Novartis, Miranti. All other authors have declared no conflicts of interest.