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Sci Rep. 2017 Aug 17;7(1):8540. 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.

Author information

1
Department of Medical Oncology, Pitié-Salpêtrière Hospital, Paris, France.
2
University Pierre and Marie Curie, Institut Universitaire de Cancérologie, Paris, France.
3
University Pierre and Marie Curie, INSERM UMRS 1136, Paris, France.
4
Department of Urology, GRC5, Pitié-Salpêtrière Hospital, 75013, Paris, France.
5
Department of Pathology, Tenon Hospital, HUEP, Paris, France.
6
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
7
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8
Department of Medical Oncology, Pitié-Salpêtrière Hospital, Paris, France. gabriel.malouf@aphp.fr.
9
University Pierre and Marie Curie, Institut Universitaire de Cancérologie, Paris, France. gabriel.malouf@aphp.fr.

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.

PMID:
28819235
PMCID:
PMC5561098
DOI:
10.1038/s41598-017-08363-6
[Indexed for MEDLINE]
Free PMC Article

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