Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma

Abstract : Prediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression. We identified prognostic lncRNAs in a training set of 351 localized ccRCCs from The Cancer Genome Atlas and validated lncRNA-based recurrence classification in an independent cohort of 167 localized ccRCCs. We identified lncRNA MFI2-AS1 as best candidate in the training set. In the validation cohort, MFI2-AS1 expression was independently associated with shorter disease-free survival (Hazard Ratio (HR) for relapse 3.5, p = 0.0001). Combined with Leibovich classification, MFI2-AS1 status improved prediction of recurrence (C-index 0.70) compared to MFI2-AS1 alone (0.67) and Leibovich classification alone (0.66). In patients with aggressive tumors (Leibovich ≥5), MFI2-AS1 expression was associated with dramatically increased risk of relapse (HR 12.16, p < 0.0001) compared to patients with undetectable MFI2-AS1 who had favorable outcomes. Compared to normal samples, MFI2-AS1 was upregulated in tumor tissue, and higher expression was associated with metastatic dissemination. Overall, MFI2-AS1 status improves patient stratification in localized ccRCC, which supports further integration of lncRNAs in molecular cancer classifications.
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Soumis le : mardi 5 septembre 2017 - 10:07:43
Dernière modification le : jeudi 7 septembre 2017 - 01:09:50

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Ronan Flippot, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, et al.. Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma. Scientific Reports, Nature Publishing Group, 2017, 7, pp.8540. 〈10.1038/s41598-017-08363-6〉. 〈hal-01581774〉

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