Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer

Abstract

The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4–6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

“…It has been reported that miR-92a-3p promotes the occurrence and development of tumors in some malignant diseases. Furthermore, Xiao et al found that expression of exosomal miR-92a-3p could predict the response to first-line chemotherapy in colorectal cancer, as biomarkers, resonating with our observations in adenomyosis 21 .…”

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

“…Further studies on the underlying mechanisms of CRC initiation and progression are required to reduce mortality caused by this neoplasia. Undoubtedly, abnormal expression of miRNAs correlates with CRC pathological stage and prognosis [43][44][45][46].…”

Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration

“…Kjersem et al [ 133 ] evaluated miRNA expression in plasma samples from 24 metastatic CRC patients, discovering that 3 miRNAs (miR-106a, miR-484, and miR-130b) were significantly more expressed in non-responders than in responders to oxaliplatin-based treatments. Gherman et al [ 134 ] reported that elevated exosomal expression of miR-92a-3p and miR-221-3p might indicate resistance to first-line chemotherapy and was linked to shorter OS. A recent review highlighted various miRNAs that potentially influence 5-fluorouracil resistance, including miR10b, miR-19b, miR-20a, miR-21, miR-23a, miR-31, miR-34, miR-129, miR-140, miR-145, miR-192, miR-215, the miR-200 family, and miR-451 [ 1 ].…”