Determining the diagnostic value of miRNA-۲۲۱ in colorectal cancer surgery

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 RNU۶B small nuclear RNA (U۶). Due to this, we include cel-miR-۳۹ as a spike-in (۲ ۱۰۸ transcripts) as an exogenous normalizer and miR-۱۶-۵p as an endogen normalizer based on prior research on exosomal miRNA normalization.Results: We examined the expression of these microRNAs in ۱۷ patients under the FOLFIRI (FIRI) protocol and ۱۴ patients under the FOLFOX (FOX) protocol at ۲ 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-۹۲a-۳p, miR-۱۴۶a-۵p, miR-۲۲۱-۳p, and miR-۴۸۴ 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-۱۴۳-۳p and miR-۲۲۱-۳p at the start of therapy have a predictive value for shorter OS, whereas increased exosomal levels of miR-۹۲a-۳p and miR-۴۸۶-۵p are associated with lower OS and PFS۱.

Keywords:

miRNA-۲۲۱ , miRNAs , colorectal cancer , Surgery