Year: 2015
Type: article
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.
Source: British Journal of Cancer
DOI: 10.1038/bjc.2015.168
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
Awards: G1760674687, G1814228702, G1967515915, G2056719604, G251590960, G2647518335, G2664172691, G3100437649, G312429407, G3173870227, Development of microRNA Biomarkers For Noninvasive Detection of Colorectal Cancer, G3411000325, G358241105, G4040562365, G526695779, North Central Cancer Treatment Group, Methylation Biomarker Development for Noninvasive Detection of Colorectal Cancer, G9000004785, G9000018464, G9000096334, G9000140428, G9000152819, G9000182627, G9000208368, G9000211914, G973482110
OpenAlex ID: W1542945320