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

Abstract

BACKGROUND:

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.

• Authors: L Perez-Carbonell, F A Sinicrope, S R Alberts, A L Oberg, F Balaguer, A Castells, C R Boland, A Goel
• Journal: British journal of cancer (Br J Cancer) Vol. 113 Issue 1 Pg. 83-90 (Jun 30 2015) ISSN: 1532-1827 [Electronic] England
• PMID: 26035698 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Biomarkers, Tumor
• MIRN320 microRNA, human
• MicroRNAs
• Organoplatinum Compounds
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (blood)
• Cohort Studies
• Colorectal Neoplasms (blood, drug therapy, physiopathology)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Male
• MicroRNAs (blood)
• Middle Aged
• Organoplatinum Compounds (therapeutic use)
• Prognosis