Earlier diagnosis and optimisation of treatment strategies for colorectal cancer (CRC) are two major areas that could improve CRC-related morbidity and mortality in New Zealand. miR-21 and miR-29a are extracellular vesicle (EV) associated microRNAs that are aberrantly expressed in tumour tissue and plasma of patients with CRC. This study has investigated these EV-miRNAs as biomarkers in the plasma and lymph nodes of CRC patients in a New Zealand cohort.
Plasma miR-21 and miR-29a levels were measured by RT-qPCR in healthy controls (n=17) and patients with early (stage I/II, n=32) vs. late disease (stage III/IV, n=29). Additionally, expression levels of miR-21 and miR-29a (RT-qPCR) and a CRC-EV protein marker (CD147; immunohistochemistry) were examined in the lymph nodes of 13 stage II CRC cancer patients to assess whether evidence of CRC-derived EVs were detectable in non-metastatic patients. Finally, expression levels of plasma miR-21 and miR-29a at baseline were correlated to clinical measures including CEA levels and tumour regression.
Plasma miR-29a expression was significantly different across patient groups (p=0.0035, one-way ANOVA) and between control vs late stage CRC and early vs late stage CRC (p<0.5, Tukey’s multiple comparison). Additionally, plasma miR-21 expression trended towards statistical significance (p=0.07, one-way ANOVA). miR-21 and CD147 were overexpressed in tumour tissue of stage II patients (50% overexpression of miR-21, 80% overexpressed CD147) and detectable at variable levels in matched lymph node samples. This work suggests that miR-29a and miR-21 could be useful markers for the discrimination of CRC patients vs controls and early vs late stage disease.