MiR-320e is a novel prognostic biomarker in colorectal cancer

L. Perez-Carbonell, F. A. Sinicrope, S. R. Alberts, A. L. Oberg, F. Balaguer, A. Castells, C. R. Boland, A. Goel

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Advances in early detection and treatment have improved outcomes in patients with colorectal cancer (CRC). However, there remains a need for robust prognostic and predictive biomarkers. We conducted a systematic discovery and validation of microRNA (miRNA) biomarkers in two clinical trial cohorts of CRC patients.Methods:We performed an initial 'discovery' phase using Affymetrix miRNA expression arrays to profile stage III CRC patients with and without tumour recurrence (n=50 per group) at 3-years of follow-up. All patients received adjuvant 5-fluorouracil (5-FU) plus oxaliplatin, that is, FOLFOX, treatment. During 'validation', we analysed miRNAs using qRT-PCR in an independent cohort of 237 stage II-IV CRC patients treated with 5-FU-based chemotherapy, as well as in normal colonic mucosa from 20 healthy subjects. Association with disease recurrence, disease-free survival (DFS) and overall survival (OS) was examined using Cox proportional hazard models.Results:In the discovery cohort, miR-320e expression was significantly elevated in stage III colon cancers from patients with vs without recurrence (95% confidence interval (CI)=1.14-1.42; P<0.0001). These results were then independently validated in stage II and III tumours. Specifically, increased miR-320e expression was associated with poorer DFS (hazard ratio (HR)=1.65; 95% CI=1.27-2.13; P=0.0001) and OS (HR=1.78; 95% CI=1.31-2.41; P=0.0003) in stage III CRC patients.Conclusions:In two clinical trial cohorts, a systematic biomarker discovery and validation approach identified miR-320e to be a novel prognostic biomarker that is associated with adverse clinical outcome in stage III CRC patients treated with 5-FU-based adjuvant chemotherapy. These findings have important implications for the personalised management of CRC patients.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalBritish journal of cancer
Volume113
Issue number1
DOIs
StatePublished - Jun 30 2015

Keywords

  • 5-fluorouracil
  • Micrornas
  • biomarker
  • colorectal cancer
  • expression
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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