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. 2023 Jun 25;24(13):10622.
doi: 10.3390/ijms241310622.

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

Alexandra Gherman  1   2 , Loredana Balacescu  1   3 , Calin Popa  4   5 , Calin Cainap  1   2 , Catalin Vlad  6   7 , Simona S Cainap  8   9 , Ovidiu Balacescu  1   3
Affiliations

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

Alexandra Gherman et al. Int J Mol Sci. .

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.

Keywords: biomarkers; chemotherapy; metastatic colorectal cancer; microRNA; response; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Fold change of the six miRNAs of interest (miR-92a-3p, miR143-3p, miR-146a-5p, miR-484, miR-486-5p, and miR-221-3p) in samples collected at baseline (B) and post-chemotherapy (PC) for the two therapeutic regimens administered: FOLFIRI (FIRI) and FOLFOX (FOX).
Figure 2
Figure 2
MicroRNA expression at baseline (B) presented in the (A) and post-chemotherapy (PC) presented in the (B), regardless of the therapy regimen administered in non-responder (NR) vs. responder (R) patients. The fold change for each sample was calculated relative to the PR group. * p ≤ 0.05.
Figure 3
Figure 3
MicroRNA expression in the FOLFOX (FOX) therapy regimen at baseline (B) presented in the (A), and post-chemotherapy (PC) presented in the (B). The fold change for each sample was calculated relative to the PR group. * p ≤ 0.05; ** p ≤ 0.01.
Figure 4
Figure 4
ROC curves for the investigated microRNAs at baseline (B) and post-chemotherapy (PC), regardless of the type of therapy. * p ≤ 0.05.
See this image and copyright information in PMC

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