Introduction: Our study examined the predictive value of six miRNAs of interest for evaluating treatment with FOLFOX and FOLFIRI when used as a first-line therapeutic option in managing patients with metastatic colorectal cancer in this context and considering the importance of this first-line treatment option in managing patients with metastatic CRC.

Material and Methods: We select a combination of endogenous and exogenous control miRNAs to improve the accuracy of the exosomal miRNA expression because there is currently no widely accepted best practice for exosomal miRNA normalization. Recent evidence suggests that using the same type of RNA species (miRNAs) as normalizers may be a more accurate approach than using other RNA species, such as RNU6B small nuclear RNA (U6). Due to this, we include cel-miR-39 as a spike-in (2 108 transcripts) as an exogenous normalizer and miR-16-5p as an endogen normalizer based on prior research on exosomal miRNA normalization.

Results: We examined the expression of these microRNAs in 17 patients under the FOLFIRI (FIRI) protocol and 14 patients under the FOLFOX (FOX) protocol at 2 different time points (baseline and post-chemotherapy) to determine the associations between the miRNAs of interest and the response to first-line chemotherapy. At baseline (B) and post-chemotherapy (PC), there were no statistically significant differences in microRNA expression between the two chemotherapy protocols.

Conclusion: Our findings demonstrated the discriminatory power of exosomal miR-92a-3p, miR-146a-5p, miR-221-3p, and miR-484 for non-responder patients regardless of the treatment employed. High baseline levels of these genes were associated with a lack of response to FOLFOX chemotherapy. Increased exosomal levels of miR-143-3p and miR-221-3p at the start of therapy have a predictive value for shorter OS, whereas increased exosomal levels of miR-92a-3p and miR-486-5p are associated with lower OS and PFS1.