Journal Article Research Support, Non-U.S. Gov't Epublish 23 citations
PubMed: 28819235 DOI: 10.1038/s41598-017-08363-6
Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma.
Sci Rep 7(1):8540
Authors: Ronan Flippot, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Marc-Olivier Bitker, Jérôme Parra, Christophe Vaessen, Frederick Allanic, Quentin Manach, Nizar M Tannir, David Khayat, Xiaoping Su, Gabriel G Malouf
Affiliations
- Department of Medical Oncology, Pitié-Salpêtrière Hospital, Paris, France.
- University Pierre and Marie Curie, Institut Universitaire de Cancérologie, Paris, France.
- University Pierre and Marie Curie, INSERM UMRS 1136, Paris, France.
- Department of Urology, GRC5, Pitié-Salpêtrière Hospital, 75013, Paris, France.
- Department of Pathology, Tenon Hospital, HUEP, Paris, France.
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- Department of Medical Oncology, Pitié-Salpêtrière Hospital, Paris, France.
- University Pierre and Marie Curie, Institut Universitaire de Cancérologie, Paris, France.
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.
MeSH
Cells, Neoplasms, Classification, Carcinoma, Renal Cell, Rna, Untranslated, Natural Science Disciplines, Rna, Long Noncoding, Rna
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