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

Sci Rep. 2017 Aug 17;7(1):8540. doi: 10.1038/s41598-017-08363-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cohort Studies
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding