MiR-139-5p may predict colorectal cancer recurrence
The microRNA (miRNA) miR-139-5p is able to differentiate between patients who are and are not going to experience colorectal cancer recurrence within 3 years, a new study shows.
Candidate miRNAs were identified from 100 patients with stage 3 colorectal cancer, 50 of which experienced recurrence after FOLFOX treatment. These were combined with data of 147 patients with stage 1 or 2 colorectal cancer obtained from The Central Genome Atlas (TCGA).
The expression of the candidates was studied in formalin-fixed, paraffin-embedded samples of stage 3 tumours from 24 patients with stage 3 colorectal cancer (12 with recurrence, 12 without). These were then validated against an array of other tumour and serum samples.
Microarray analysis yielded 30 miRNAS that were significantly upregulated in recurrent colorectal cancers. On the other hand, RNA-seq data from TCGA showed that 23 miRNAs were upregulated in recurrent colorectal cancer patients.
Combining these data sets resulted in five miRNAs upregulated in relapse colorectal cancer patients: let-73, miR-100, -139-5p, -181a and -181b. Of these, only miR-100 was not able to distinguish patients with vs without recurrence via Kaplan-Meier analysis.
Quantitative real-time, reverse transcription PCR (qRT-PCR) was used to measure the levels of expression of these miRNAs and showed that only the expression miR-139-5p was higher in recurrent patients, indicating that it may be used as a biomarker.
In two separate cohorts, the expression miR-139-5p was significantly higher in primary colorectal cancer tissues of patients who experienced recurrence within 3 years of surgery (p<0.05 for both). Kaplan-Meier analysis showed that those with high miR-139-5p expression had poorer recurrence-free survival.
Finally, serum levels of miR-139-5p were higher in patients who experienced recurrence compared to those who did not. Levels were also higher in stage 3 and 4 colorectal cancers compared to stage 1.