Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

Abstract

Targeting angiogenesis in the treatment of colorectal cancer (CRC) is a common strategy, for which potential predictive biomarkers have been studied. miRNAs are small non-coding RNAs involved in several processes including the angiogenic pathway. They are very stable in biological fluids, which turns them into potential circulating biomarkers. In this study, we considered a case series of patients with metastatic (m) CRC treated with a bevacizumab (B)-based treatment, enrolled in the prospective multicentric Italian Trial in Advanced Colorectal Cancer (ITACa). We then analyzed a panel of circulating miRNAs in relation to the patient outcome. In multivariate analysis, circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p resulted in being significantly associated with progression-free survival (PFS) (p = 0.027, p = 0.034 and p = 0.039, respectively) and overall survival (OS) (p = 0.044, p = 0.024 and p = 0.032, respectively). We also observed that an increase in hsa-miR-155-5p at the first clinical evaluation was significantly associated with shorter PFS (HR 3.03 (95% CI 1.06–9.09), p = 0.040) and OS (HR 3.45 (95% CI 1.18–10.00), p = 0.024), with PFS and OS of 9.5 (95% CI 6.8–18.7) and 15.9 (95% CI 8.4–not reached), respectively, in patients with an increase ≥30% of hsa-miR-155-5p and 22.3 (95% CI 10.2–25.5) and 42.9 (24.8–not reached) months, respectively, in patients without such increase. In conclusion, our results highlight the potential usefulness of circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p in predicting the outcome of patients with mCRC treated with B. In addition, the variation of circulating hsa-miR-155-5p could also be indicative of the patient survival.

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

“…Pan et al () have found low expression level of miR‐29b‐3p in serum of multiple myeloma patients. Circulating basal level of miR‐29b‐3p can predict the outcome of patients with metastatic colorectal cancer treated with bevacizumab (Ulivi et al, ). However, no papers have reported the functions of miR‐29b‐3p on II/R injury.…”

Current and New Predictors for Treatment Response in Metastatic Colorectal Cancer. The Role of Circulating miRNAs as Biomarkers

“…Ulivi and colleagues [66] also analyzed the role of circulating miRNAs in predicting the clinical outcome of 52 mCRC patients treated with a Bevacizumab-containing regimen (FOLFOX or FOLFIRI) within the ITACa clinical trial. Firstly, they analyzed the association between baseline circulating miRNAs and the clinical pathological characteristics of the patients and found hsa-miR-199a-5p, hsa-miR-335-5p and hsa-miR-520d-3p to be significantly upregulated in left-sided versus right-sided tumors and hsa-miR-21-5p and hsa-miR-221-3p significantly associated with the RAS mutational status.…”

The Dual Role of MicroRNAs in Colorectal Cancer Progression

“…In addition, research reported that miR-155 has an effect on CRC invasion metastasis. Ulivi et al pointed out circulating plasma levels of miR-155 as predictors of bevacizumab efficacy in patients with metastatic CRC, which indicated that miR-155 could be a bio-marker in the treatment used concurrently with bevacizumab [ 47 ]. Zhang et al confirmed that up-regulation of miR-155 plays an important role in promoting CRC cell migration and invasion, and acts as a mediator of EMT, through the regulation of claudin-1 expression [ 48 ].…”