MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer

Abstract

Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making.

Assessing the Role of MicroRNAs in Predicting Breast Cancer Recurrence—A Systematic Review

“…MicroRNAs act at a post-transcriptional level by binding to messenger RNA (mRNA) and influencing protein synthesis at a cellular level [ 7 ]. Recent data has illustrated the relevance of miRNA measurement to predict response to therapeutic strategies [ 7 , 8 , 9 , 10 ], enhancing cancer diagnostics [ 11 , 12 ], and predicting long-term outcomes for those diagnosed with malignancy [ 13 , 14 ]. In combination, these favourable characteristics illustrate the candidacy of miRNAs as biomarkers in the context of breast cancer research [ 15 , 16 , 17 , 18 ].…”

Rebound increase in microRNA levels at the end of 5-FU-based therapy in colorectal cancer patients

“…Even alone, they possess the characteristics of biomarkers required to stratify different sub-groups of patients based on their microsatellite instability (MSI) status 17 . Also, CRC patients with positive lymphatic invasion have been presented to have aberrant expression of miRNA21 and miRNA135b 18 .…”

Biological Implications of MicroRNAs as Regulators and Biomarkers of Therapeutic Toxicities in Breast Cancer

“…Since the seminal work of these authors, the role of miRNAs in breast cancer has been further elucidated. For example, previous authors have demonstrated the capabilities of miRNAs to predict breast cancer hormone receptor status, others have evaluated the role of miRNAs as therapeutic options in cancer [ 19 , 20 , 21 , 22 ], and several previous reports have correlated miRNA expression profiles with long-term survival outcomes in malignancy [ 23 , 24 , 25 ].…”