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

Abstract

Simple SummaryDetermining the degree of nodal involvement provides key prognostic information in several malignancies, including colorectal cancer (CRC). Furthermore, predicting long-term outcomes in such cancers often proves challenging to the multidisciplinary team. Therefore, the purpose of this translational research study was to evaluate the role of mi(cro)RNAs as biomarkers used to predict nodal status and recurrence in patients being treated for CRC. This analysis involved the quantification of miRNA targets in 74 patients with CRC using real-time reverse transcriptase polymerase chain reaction. Aberrant expression of miR-21 and miR-135b correlated with increased metastatic disease in local lymph nodes following resection. Interestingly, increased expression of miR-195 displayed strong capabilities of predicting the time to disease recurrence. These results add to the growing evidence illustrating the value of using miRNA expression profiling to inform patient outcomes in cancer. These findings may be further validated in further studies as we attempt to personalise the management paradigm for prospective patients diagnosed with CRC.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.